Outcome of positive antinuclear antibodies in individuals without connective tissue disease.
To determine if individuals with high titer antinuclear antibodies (ANA) but without clinical evidence of connective tissue disease (CTD) subsequently develop CTD or experience a change in ANA positivity. We included patients from an initial study database as well as those reviewed in an outpatient rheumatology clinic at the University of Alberta Hospital over the past 8 years. A telephone survey targeting signs and symptoms of CTD was conducted. Serum samples from consenting patients were then assayed for ANA, antibodies to extractable nuclear antigens (ENA), and anti-dsDNA by the Rheumatic Disease Unit at the University of Alberta Hospital. Sixty-two patients completed the telephone survey and 53 completed both the telephone survey and repeat serological blood investigations. Mean length of followup was 5.4 years, with an age range from 19 to 87 years. Forty-eight of 53 patients (91%) remained ANA positive on repeat testing, and 5 patients were also ENA positive. Three patients had been diagnosed with CTD since the previous study. The most common clinical features on telephone survey included joint pain (34 patients) followed by Raynaud's phenomenon (11 patients). Patients tended to remain ANA positive on repeat testing. Three out of 53 patients had developed CTD, reflecting the more sensitive but less specific nature of ANA testing. Another common condition associated with ANA positivity was hypothyroidism. Continued longterm followup with larger cohorts is needed.


Bioconversion of high concentrations of hydrogen sulfide to elemental sulfur in airlift bioreactor.
Several bioreactor systems are used for biological treatment of hydrogen sulfide. Among these, airlift bioreactors are promising for the bioconversion of hydrogen sulfide into elemental sulfur. The performance of airlift bioreactors is not adequately understood, particularly when directly fed with hydrogen sulfide gas. The objective of this paper is to investigate the performance of an airlift bioreactor fed with high concentrations of H2S with special emphasis on the effect of pH in combination with other factors such as H2S loading rate, oxygen availability, and sulfide accumulation. H2S inlet concentrations between 1,008 ppm and 31,215 ppm were applied and elimination capacities up to 113 g H2S m(-3) h(-1) were achieved in the airlift bioreactor under investigation at a pH range 6.5-8.5. Acidic pH values reduced the elimination capacity. Elemental sulfur recovery up to 95% was achieved under oxygen limited conditions (DO < 0.2 mg/L) and at higher pH values. The sulfur oxidizing bacteria in the bioreactor tolerated accumulated dissolved sulfide concentrations >500 mg/L at pH values 8.0-8.5, and near 100% removal efficiency was achieved. Overall, the resident microorganisms in the studied airlift bioreactor favored pH values in the alkaline range. The bioreactor performance in terms of elimination capacity and sulfur recovery was better at pH range 8-8.5.


Cigarettes and cigarette smoking.
Tobacco use was widespread in the New World by the time of the first voyage of Columbus; however, it is only in the last century that the use of tobacco as cigarettes has been prevalent. The milder tobacco and more acidic smoke of cigarettes lead to the deeper inhalation of tobacco into the lung with resultant deposition and absorption of the addicting, toxic, and carcinogenic components of the smoke. More than 4000 individual constituents have been identified in cigarette smoke, and the relative concentrations of these constituents vary widely between brands of cigarettes. Tar yield, a measure of the total particulate matter of the smoke, varies markedly with the characteristics of the cigarette manufacture and with the pattern of inhalation. As a result, tar is not a good measure of the dose of toxic or carcinogenic agents received by the individual smoker. The particle size of cigarette smoke is in the range that will lead to deposition in the airways and alveoli of the lung, and many of the gas-phase constituents are absorbed across the alveolar capillary membrane. The irritant agents in the smoke cause acute and chronic changes in lung structure and function that may result in greater retention of carcinogens within the lung and increased vulnerability of the lung to the effects of these carcinogens. Carcinogens and other constituents of cigarette smoke are also absorbed into the blood and metabolized to active forms through microsomal enzyme systems induced by cigarette smoke. The cellular influx of neutrophils and alveolar macrophages that is part of the inflammatory response may be the precursor of the alveolar wall destruction that results in emphysema. The prevalence of smoking is not uniformly distributed across the population. Men began smoking in large numbers very early in the century, but women began to smoke in large number only at the time of the Second World War. Men born after 1930 have been less likely to take up smoking than their older counterparts. The prevalence of smoking is currently declining in both men and women.


Revisiting the Labial Pit Organ Pathway in the Noctuid Moth, Helicoverpa armigera.
Lepidopteran species detect CO2 via a specialized organ located on the peripheral segment of the labial palps, the labial palp pit organ (LPO). Based on tracing of LPO sensory neurons targeting one distinct antennal-lobe glomerulus, Kent and her colleagues described the projections originating from the LPO in the sphinx moth as "an accessory olfactory pathway in Lepidoptera" already in the 1980 ties. In spite of similar reports from studies of other lepidopteran species, however, it has been an unresolved issue whether additional termination areas of the labial nerve, such as the gnathal ganglion (GNG) and the ventral nerve cord, are actually output sites of LPO neurons. Since the previous studies have interpreted slightly differently about the projection pattern occurring from the classical mass staining, we performed selective mass staining from the inside of the pit and from the outer surface of the peripheral palp. The results demonstrated that the LPO sensory neurons project exclusively to the LPO glomerulus (LPOG), whereas the non-LPO sensory neurons target the GNG and the ventral nerve cord. Additional iontophoretic staining of individual LPO sensory neurons, performed from the LPO and the LPOG, showed three morphological neuron types: one bilateral targeting the LPOG in both antennal lobes, one unilateral targeting the ipsilateral LPOG only, and one contralateral targeting the LPOG in the other antennal lobe. Finally, to explore putative differences in the projection pattern of neurons housed by two previously reported sensillum types in the pit, i.e., hair-shaped sensilla located distally and club-shaped sensilla located proximally, we performed mass staining from two different levels of the peripheral palp. We found a projection pattern implying stronger innervation of the ipsi- than the contralateral LPOG in both staining experiments.


Behavior change interventions to prevent HIV infection among women living in low and middle income countries: a systematic review.
We conducted a systematic review of behavioral change interventions to prevent the sexual transmission of HIV among women and girls living in low- and middle-income countries. PubMed/MEDLINE, Web of Science, the Cochrane Library, and other databases and bibliographies were systematically searched for trials using randomized or quasi-experimental designs to evaluate behavioral interventions with HIV infection as an outcome. We identified 11 analyses for inclusion reporting on eight unique interventions. Interventions varied widely in intensity, duration, and delivery as well as by target population. Only two analyses showed a significant protective effect on HIV incidence among women and only three of ten analyses that measured behavioral outcomes reduced any measure of HIV-related risk behavior. Ongoing research is needed to determine whether behavior change interventions can be incorporated as independent efficacious components in HIV prevention packages for women or simply as complements to biomedical prevention strategies.


Ligand based drug design of new heterocyclic imines of GABA analogues: A molecular docking approach for the discovery of new GABA-AT inhibitors.
Degradation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) is mainly catalysed by GABA aminotransferase (GABA-AT), excessive activity of which leads to convulsions. Inhibition of GABA-AT increases the concentration of GABA and can terminate the convulsions. Several studies have revealed that GABA analogues could be the outstanding scaffolds for the design of potent inhibitors of GABA-AT. The poor ability of GABA analogues to cross the blood-brain barrier (BBB), always produces low therapeutic index. However, Vigabatrin, a mechanism-based inhibitor of GABA-AT, is currently approved treatment of epilepsy, but it has harmful side effects, leaving a need for improved GABA-AT inactivators. In our present in silico investigation, AutoDock 4.2,-based on Lamarckian genetic algorithm was employed for virtual screen of a compound library with 35 entries (Schiff's bases of GABA) in search for novel and selective inhibitors of GABA-AT. By means of flexible type of molecular docking, we proposed that these designed molecules could successfully bind into the active pocket of GABA-AT with good predicted affinities in comparison to standard vigabatrin. Among the designed analogues, HIG18, HIG28 and HIG30 showed significant binding free energy of -10.25, -9.88 and -9.31 kcal/mol with predicted inhibitory constant values of 0.03, 0.05 and 0.15 µM respectively. Using ligand-based drug design, we proposed that electron withdrawing phenyl substituted heterocyclic imines of GABA could be considered as promising structures for synthesis and testing of new GABA-AT inhibitors from this class. We hypothesize that novel GABA analogues with an azomethine linkage incorporated with heterocyclic system can have increased affinity and more lipophilic character that would provide a probability of having less toxic effect in the therapy of convulsions.


CB1 antagonism: interference with affective properties of acute naloxone-precipitated morphine withdrawal in rats.
Modulation of the endocannabinoid system has been found to interfere with opiate withdrawal. The potential of activation and blockade of the endocannabinoid system to prevent the aversive-affective state of naloxone-precipitated morphine withdrawal (MWD) was investigated in a one-trial conditioned place aversion (CPA) paradigm. CPA provides a sensitive measure of the motivational effects of acute MWD. The potential of the fatty acid amide hydrolase (FAAH) inhibitors, URB597 and PF-3845, the CB1 antagonist/inverse agonist, AM251, and the neutral CB1 antagonists, AM4113 and AM6527 (oral), to interfere with establishment of a MWD-induced CPA was investigated. As well, the potential of AM251 and AM4113 to interfere with reinstatement of a previously established MWD-induced CPA was investigated. Using a one-trial place conditioning paradigm, rats were administered naloxone (1 mg/kg, subcutaneous (s.c.)) 24 h after receiving a high dose of morphine (20 mg/kg, s.c.) and were placed on the conditioning floor. To determine the effect of each pretreatment drug on the establishment of the MWD-induced CPA, URB597 (0.3 mg/kg, intraperitoneally (i.p.)), PF-3845 (10 mg/kg, i.p.), AM251 (1 or 2.5 mg/kg, i.p.), AM4113 (1 or 2.5 mg/kg, i.p.), and AM6527 (5 mg/kg, oral) were administered prior to conditioning. AM251 (2.5, but not 1 mg/k), AM4113, and AM6527, but not URB597 or PF-3845, interfered with the establishment of the MWD-induced CPA. AM251 and AM4113 did not prevent reinstatement of the CPA. Neutral antagonism of the CB1 receptor reduces the aversive affective properties of morphine withdrawal.


Protective effects of N-acetylcysteine on noise-induced hearing loss in guinea pigs.
Increasing evidence suggests the involvement of oxidative stress in noise-induced hearing loss. The present study analysed, in an animal experimental model, the time course of the pathogenic mechanisms of noise-induced cochlear damage and the efficacy of the antioxidant drug N-acetylcysteine in reducing noise ototoxicity. Animals were divided into two groups, exposed to noise one treated with N-acetylcysteine for 3 days and one (the control group) with saline. Acoustic trauma was induced by a continuous pure tone of 6 kHz, at 120 dB SPL for 30 minutes. Electrocochleographic recordings were made from an implanted round window electrode and the compound action potentials were measured daily at 2-16 kHz for 7 days. Morphological changes were analysed by scanning electron microscopy. The acoustic threshold measured 1 hour after acoustic trauma was elevated in the control group to 70-90 dB in the higher frequencies of the compound action potential audiogram, with a maximum threshold elevation ranging between 12 and 16 kHz. During the first 24 h, following acoustic trauma, there was a partial recovery of compound action potential thresholds of about 20 dB to reach a final threshold elevation of about 50-70 dB; there was no further improvement over the remaining experimental week. Animals treated with N-acetylcysteine showed a similar temporary threshold shift but a clear improvement in the recovery of compound action potential thresholds, with significantly reduced permanent threshold shift and hair cell loss. These data suggest that N-acetylcysteine is able to attenuate the toxic effect of acoustic trauma and could represent an interesting molecule for preventing inner ear injuries.


Natural variations and genome-wide association studies in crop plants.
Natural variants of crops are generated from wild progenitor plants under both natural and human selection. Diverse crops that are able to adapt to various environmental conditions are valuable resources for crop improvements to meet the food demands of the increasing human population. With the completion of reference genome sequences, the advent of high-throughput sequencing technology now enables rapid and accurate resequencing of a large number of crop genomes to detect the genetic basis of phenotypic variations in crops. Comprehensive maps of genome variations facilitate genome-wide association studies of complex traits and functional investigations of evolutionary changes in crops. These advances will greatly accelerate studies on crop designs via genomics-assisted breeding. Here, we first discuss crop genome studies and describe the development of sequencing-based genotyping and genome-wide association studies in crops. We then review sequencing-based crop domestication studies and offer a perspective on genomics-driven crop designs.


Use of automated patch clamp in cardiac safety assessment: Past, present & future perspectives.
There is no doubt that automated patch clamp (APC) technology has revolutionized research in biomedical science. High throughput ion channel screening is now an integral part of the development and safety profiling of the majority of new chemical entities currently developed to address unmet medical needs. The increased throughput it provides has significantly improved the ability to overcome the time-consuming, low throughput bottlenecks resulting from the more conventional manual patch clamp method, considered the 'gold standard', for studying ion channel function and pharmacology. While systems offering the luxury of automation have only been commercially available for two decades, the road leading to this new technology is long and rich in seminal, hands-on, studies dating back as far as the 18th century. So where does this technology currently stand, and what will it look like in the future? In the current article, we review the scientific history leading to the development of APC systems, examine key drivers in the rapid development of this technology (such as failed ion channel programmes and the issue of drug-induced hERG inhibition and QT interval prolongation), highlight key capabilities and finally provide some perspective on the current and future impact of the technology on cardiac safety assessment and biomedical science.


Immunohistochemical expression of ghrelin in capsaicin-treated rat ovaries during the different developmental periods.
Red hot pepper is a plant that belongs to the Solanaceae family and is known as Capsicum annuum. Capsaicin is the active ingredient of cayenne pepper. Ghrelin is a hormone, which consists of polypeptide structure. Ghrelin also contributes to growth hormone secretion, energy balance, food intake and body weight regulator. The aim of this study was the localization and expression of ghrelin in the ovaries of rats treated with capsaicin during the postnatal development. Ninety female Sprague-Dawley rats (21 d) were used. The rats were randomly divided into 3 groups (n=30 each) as pubertal, post pubertal and adult. Each group was subdivided into three groups. The first subgroup (control) was given no injections. The second subgroup (vehicle) received only 0.3 cc solvent and the third subgroup (experiment) received subcutaneous injection of equal volume of capsaicin (1 mg/kg/d) for 42, 56, and 70 days. Ghrelin immunoreactivity was determined in ovarian follicular granulosa cells, interstitial cells and corpus luteal cells. A ghrelin immunopositive reaction located in the cytoplasm of cells in all groups. These results indicate that prolonged administration of low dose capsaicin does not affect ghrelin expression. However, follicular atresia was seen in lower rate in capsaicin treated group in comparison to other groups.


Bone marrow stromal cells transduced with human hemangiopoietin gene support hematopoiesis in vitro.
The aim of this study was to construct a eukaryotic expression vector containing human hemangiopoietin (hHAPO) gene and express it in mouse bone marrow stromal cell line HESS-5, then support hematopoiesis in vitro with gene-modified HESS-5 (hHAPO-HESS-5). The polymerase chain reaction (PCR) products of HAPO were digested with BamHI and BgII. Then the HAPO gene segment obtained was again cloned into pIRES2-EGFP to construct recombinant eukaryotic expression vector HAPO-pIRES2-EGFP. The recombinant vector was identified by enzyme digestion analysis, PCR, and sequencing. HESS-5 cells were transformed by recombinant vector and positive clones were selected with G418. The expression of HAPO gene in the transformed cells was detected by studying EGFP expression, reverse transcription (RT)-PCR, and Western-blotting analysis. Support of human hematopoiesis by hHAPO-HESS-5 cells was evaluated in co-culture experiments with human CD34+ cells. Enzyme digestion analysis and sequencing showed that the target gene had been cloned into the recombinant vector. The expression of HAPO gene in the transformed stromal cells was demonstrated by fluoro-microscopy and RT-PCR analysis. HAPO protein was also detected in the supernatant of hHAPO-HESS-5 by Western blot analysis. As expected, stably transfected hHAPO-HESS-5 cells significantly increased in both relative and absolute numbers of CD34+ cells after 14 days of culture. The PKH26 study demonstrated that cell division was faster in CD34+ cells co-cultured with hHAPO-HESS-5 cells than in cells cocultured with vector-HESS-5 cells. The hHAPO-HESS-5 cells also supported human hematopoiesis in vitro more efficiently than did control vector-HESS-5 cells. A recombinant eukaryotic expression vector has been constructed and expressed successfully in transformed cells. The hHAPO-HESS-5 cells support rapid generation of primitive progenitor cells and maintain reconstituting ability of hematopoietic stem cells in vitro. Therefore, it would be possible to use stromal cells expressing HAPO gene as seed cells in the bone marrow transplantation.


Phospholipids and nuclear RNA.
It has been demonstrated that in hepatocyte nuclei the chromatin phospholipid fraction is localized near the RNA in decondensed chromatin. The aim of the present study was to see if there is any linkage between phospholipids and other nuclear components. Isolated hepatocyte nuclei and nuclear membranes were treated with deoxyribonuclease and ribonuclease. No loss of phospholipids was observed after DNA digestion, whereas 48% was lost following enzymatic RNA removal. This loss of phospholipids, localized either near the membrane or inside the nucleus, was not homogeneous for all phospholipids: phosphatidylserine and sphingomyelin being the most affected. It can be concluded that 48% of nuclear phospholipids, in particular sphingomyelin, is lost with RNA removal. This result is discussed in view of a possible role of phospholipids in DNA synthesis and RNA transcription.


Use of sleep aids during the first year of life.
In an attempt to foster self-soothing during the night, a novel sleep aid infused with maternal odor was introduced to 4 groups of infants ranging in age from 3 to 12 months. Infants' use of parent-provided sleep aids also was examined. Nighttime sleep and waking behaviors were videotaped for 2 consecutive nights on 3 occasions over a 3-month interval. Using all-night video recording, the study examined the infant's use of a novel sleep aid and parent-provided sleep aids during sleep onset and after nighttime awakenings. Results indicated that infants of different ages differed in the types of sleep aids used when falling asleep either at the beginning of the night or after awakenings in the middle of the night. More 3-month-olds used their thumbs/fingers/hands, whereas more 6-month-olds used soft objects. The 6-month-olds were most likely to use the novel sleep aid. Almost all of the infants at all 4 ages used some type of object during the night. Intra-individual analyses showed that infants tended to change their pattern of sleep aid use over the 3-month study period. The data provide evidence that infants during the first year of life use sleep aids frequently and interchangeably rather than a specific favorite object.


Severe myalgia of the lower extremities as the first clinical feature of meningococcal purpura fulminans.
In patients with meningococcal infection, devastating presentations, such as purpura fulminans, which can progress to extensive tissue necrosis of the limbs and digits, have a significant social impact. The case presented herein illustrates such a phenomenon in a patient who developed bilateral necrosis of the lower extremities as a result of infection with Neisseria meningitis. We emphasize that severe myalgia was the first clinical manifestation of meningococcal purpura fulminans in our case. However, myalgia has typically been overlooked and undervalued as an early clinical feature of meningococcal sepsis. Early recognition and prompt initial antibiotic therapy continue to be the cornerstones of the successful management of this dramatic disease, reducing morbidity and mortality.


On-chip analysis, indexing and screening for chemical producing bacteria in a microfluidic static droplet array.
Economic production of chemicals from microbes necessitates development of high-producing strains and an efficient screening technology is crucial to maximize the effect of the most popular strain improvement method, the combinatorial approach. However, high-throughput screening has been limited for assessment of diverse intracellular metabolites at the single-cell level. Herein, we established a screening platform that couples a microfluidic static droplet array (SDA) and an artificial riboswitch to analyse intracellular metabolite concentration from single microbial cells. Using this system, we entrapped single Escherichia coli cells in SDA to measure intracellular l-tryptophan concentrations. It was validated that intracellular l-tryptophan concentration can be evaluated by the fluorescence from the riboswitch. Moreover, high-producing strains were successfully screened from a mutagenized library, exhibiting up to 145% productivity compared to its parental strain. This platform will be widely applicable to strain improvement for diverse metabolites by developing new artificial riboswitches.


Effect of ionic liquids on the interaction between liposomes and common wastewater pollutants investigated by capillary electrophoresis.
The effect of three phosphonium and imidazolium ionic liquids (ILs) on the interaction between liposomes and common pharmaceuticals found in wastewaters was studied. The liposomes comprised zwitterionic phosphatidyl choline and negatively charged phosphatidyl glycerol. A set of common cationic, anionic, and neutral compounds with varying chemical composition and unique structures were included in the study. The electrophoretic mobilities of the analytes were determined using conventional capillary electrophoresis (CE), using CE under reversed electroosmotic flow mobility conditions, and in the presence of ILs in the background electrolyte (BGE) solution by electrokinetic chromatography (EKC). In order to evaluate the impact of ILs on the interaction between the compounds and the liposomes, EKC was performed with liposome dispersions, with and without ILs. The retention factors of the compounds were calculated using BGEs including liposome dispersions with and without ILs. Two phosphonium based ILs, namely tributyl(tetradecyl)phosphonium chloride ([P14444]Cl) and octyltributylphosphonium chloride ([P8444]Cl), were chosen due to their long alkyl chains and their low aggregation concentrations. Another IL, i.e. 1-ethyl-3-methylimidazolium acetate ([emim][OAc]), was chosen based on our previous study, which suggests that it has a minimal or even nonexistent effect on liposomes at the used concentrations. The results indicate that the studied ILs have an effect on the interactions between wastewater compounds and liposomes, but the effect is highly dependent on the concentration of the IL and on the IL alkyl chain lengths. Most of the ILs hindered the interactions between the liposomes and the compounds, indicating strong interaction between ILs and liposomes. In addition, the nature of the studied compounds themselves affected the interactions.


Dapsone-induced peripheral neuropathy. Case report and review.
A severe motor and a minor sensory neuropathy developed in a man being treated with dapsone (4,4'-diaminodiphenylsulfone) for dermatitis herpetiformis. He had received dapsone for 16 years before any signs of neurotoxicity became evident. Electrodiagnostic and clinical features were consistent with an axonal neuropathy. Clinical characteristics of dapsone-induced neuropathy include a motor neuropathy affecting the extremities, usual onset within five years after the initiation of dapsone therapy, dapsone dosage usually equal to or greater than 300 mg/day, and, almost always, complete recovery from the neuropathy after dapsone-dose reduction or withdrawal. The patient was found to be a slow acetylator of sulfamethazine, and therefore is a slow acetylator of dapsone. An HLA typing was done on the patient. New cases of dapsone-induced neuropathy should be HLA typed and have acetylation profiles in an attempt to identify future high-risk patients. This case is noteworthy for the length of time of dapsone usage (16 years) and the low daily dosage of dapsone (100 mg) taken prior to the development of neuropathy.


Psychological treatments for adults and children with epilepsy: Evidence-based recommendations by the International League Against Epilepsy Psychology Task Force.
Given the significant impact that psychosocial factors and epilepsy treatments can have on the health-related quality of life (HRQOL) of individuals with epilepsy and their families, there is great clinical interest in the role of psychological evaluation and treatments to improve HRQOL and comorbidities. Therefore, the International League Against Epilepsy (ILAE) charged the Psychology Task Force with the development of recommendations for clinical care based on evaluation of the evidence from their recent Cochrane review of psychological treatments in individuals with epilepsy. The literature search for a recent Cochrane review of randomized controlled trials investigating psychological treatments for individuals with epilepsy constitutes the key source of evidence for this article. To provide practical guidance to service providers, we provide ratings on study research designs based on (1) the American Academy of Neurology's Level of Evidence system and (2) the Grading of Recommendations, Assessment, Development, and Evaluation system. This paper is the culmination of an international collaboration process involving pediatric and adult psychologists, neurologists, psychiatrists, and neuropsychiatrists. The process and conclusions were reviewed and approved by the ILAE Executive Committee. The strongest evidence for psychological interventions was identified for the most common mental health problems, including depression, neurocognitive disturbances, and medication adherence. Psychological interventions targeting the enhancement of HRQOL and adherence and a decrease in comorbidity symptoms (anxiety, depression) should be incorporated into comprehensive epilepsy care. There is a range of psychological strategies (ie, cognitive behavioral therapy and mindfulness-based therapies) that show promise for improving the lives of persons with epilepsy, and clinical recommendations are provided to assist epilepsy health care providers in treating the comorbidities and challenges associated with epilepsy and its treatments.


ABSL-4 aerobiology biosafety and technology at the NIH/NIAID integrated research facility at Fort Detrick.
The overall threat of a viral pathogen to human populations is largely determined by the modus operandi and velocity of the pathogen that is transmitted among humans. Microorganisms that can spread by aerosol are considered a more challenging enemy than those that require direct body-to-body contact for transmission, due to the potential for infection of numerous people rather than a single individual. Additionally, disease containment is much more difficult to achieve for aerosolized viral pathogens than for pathogens that spread solely via direct person-to-person contact. Thus, aerobiology has become an increasingly necessary component for studying viral pathogens that are naturally or intentionally transmitted by aerosol. The goal of studying aerosol viral pathogens is to improve public health preparedness and medical countermeasure development. Here, we provide a brief overview of the animal biosafety level 4 Aerobiology Core at the NIH/NIAID Integrated Research Facility at Fort Detrick, Maryland, USA.


Ultrasound-guided medial branch of the superior laryngeal nerve block to reduce peri-operative opioids dosage and accelerate patient recovery.
To explore whether the medial branch block of superior laryngeal nerve can reduce the stress response of patients undergoing intubation and further reduce the dosage of opioids. 80 patients undergoing gynecological laparoscopic surgery were selected, and randomly divided into 4 groups. All patients in the experimental groups received bilateral internal branch of superior laryngeal nerve block and transversus abdominis plane block. But the dosage of sufentanil used for anesthesia induction in the group A, B, and C was 0.4, 0.2, and 0μg/kg, respectively. Group D do not underwent supralaryngeal nerve block and the dosage of sufentanil was 0.4μg/kg. The heart rate (HR) and mean arterial pressure(MAP) were recorded at the time of entering the operating room(T1), before intubation after induction(T2), immediately after intubation(T3), 5min after intubation(T4), before extubation(T5), immediately after extubation(T6), 5min after extubation(T7). We also recorded the stay time in the recovery room, the number of cases of postoperative sore throat, the number of cases of nausea and vomiting, the first intestinal exhaust time, the length of hospital stay after operation. The HR of group A, C and D at T3 was significantly higher than that at T2(P < 0.01), while the HR of group B had no significant change. The HR of group A, C and D at T4 was lower than that at T3(P < 0.01), while the HR of group B had no obvious change. The HR of group C and D at T3 was significantly higher than that at T1 (P < 0.01). The MAP of group A and D at T4 was significantly lower than that at T1 (P<0.001). The first postoperative intestinal exhaust time in group A, B and C was significantly shorter than that in group D. The length of hospital stay after operation in group B and C was shorter than that in group D. Ultrasound-guided superior laryngeal nerve block combined with 0.2μg/kg sufentanil can reduce the intubation reaction, have better hemodynamic stability, reduce the first postoperative intestinal exhaust time and postoperative hospital stay, thereby accelerating the postoperative recovery of patients.


In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5 T.
Cardiac echo-planar imaging suffers invariably from regions of severe distortion and T*2 decay in the myocardium. The purpose of this work was to perform local measurements of T*2 and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*2 were measured in five normal volunteers in short-axis slices spanning from base to apex. It was found that T*2 ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*2 in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70-100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.


Body mass index and risk of stroke and myocardial infarction in a relatively lean population: meta-analysis of 16 Japanese cohorts using individual data.
The association of overweight/obesity with the incidence of cardiovascular diseases, especially stroke, has not been comprehensively examined in relatively lean populations in which stroke is more prevalent than coronary heart disease. Pooled individual data from 16 Japanese cohorts comprising 45 235 participants ages 40 to 89 years without previous history of cardiovascular disease were studied. During follow-up, 1113 incident strokes and 190 myocardial infarctions were identified. At baseline, mean ages of men and women were 55.4 and 56.5 years and mean body mass indices (BMI) were 23.0 and 23.4 kg/m(2), respectively. Compared with those with BMI <21.0, incidence rates of cerebral infarction in subjects with BMI ≥ 27.5 were significantly elevated in both men (hazard ratio, 1.81; 95% confidence interval [CI], 1.28 to 2.56) and women (hazard ratio, 1.65; 95% CI, 1.23 to 2.21), adjusted for age, smoking, and drinking habit. Incidence of cerebral hemorrhage was also associated positively with BMI in both men (hazard ratio, 2.51; 95% CI, 1.21 to 5.20) and women (hazard ratio, 1.98; 95% CI, 1.12 to 3.52). Adjustment for systolic blood pressure, a mediating factor, significantly attenuated most BMI association with stroke in both sexes. For myocardial infarction, the hazard ratio was 3.16 (95% CI, 1.66 to 6.01) for BMI 27.5 or greater versus less than 21.0 only in men, which appeared partly mediated by total cholesterol and SBP. Overweight/obesity was associated with an increased risk of cerebral infarction and hemorrhage in men and women and myocardial infarction in men. Weight control may have the potential to prevent both stroke and myocardial infarction in Japan.


The integral divalent cation within the intermolecular purine*purine. pyrimidine structure: a variable determinant of the potential for and characteristics of the triple helical association.
In vitro assembly of an intermolecular purine*purine.pyrimidine triple helix requires the presence of a divalent cation. The relationships between cation coordination and triplex assembly were investigated, and we have obtained new evidence for at least three functionally distinct potential modes of divalent cation coordination. (i) The positive influence of the divalent cation on the affinity of the third strand for its specific target correlates with affinity of the cation for coordination to phosphate. (ii) Once assembled, the integrity of the triple helical structure remains dependent upon its divalent cation component. A mode of heterocyclic coordination/chelation is favorable to triplex formation by decreasing the relative tendency for efflux of integral cations from within the triple helical structure. (iii) There is also a detrimental mode of base coordination through which a divalent cation may actively antagonize triplex assembly, even in the presence of other supportive divalent cations. These results demonstrate the considerable impact of the cationic component, and suggest ways in which the triple helical association might be positively or negatively modulated.


[Disclosing a diagnosis of Alzheimer's disease].
How many practitioners do inform their patients about the diagnosis of Alzheimer's disease? Does this announcement increase the risk of depression and/or suicide or in the contrary the compliance to the care? Do the caregivers want that the information will be gave to their parents? In the case where the caregivers could present Alzheimer's disease, do they want to know their diagnosis? The arguments pro- or contra- the announcement of the diagnosis to the patients are discussed then a strategy of announcement is proposed in order to give a clear message to the patient, his family and caregivers. A pluridisciplinary approach is essential. Empathy is the optimal professional attitude in front of the emotional reactions secondary to the announcement. The announcement of the diagnosis produces rather a positive impact but the risks have to be appreciated and controlled. The announcement of the diagnosis represents a comprehensive medical act which demands a technical approach.


Defensin promotes the binding of lipoprotein(a) to vascular matrix.
Retention of lipoproteins within the vasculature is a central event in the pathogenesis of atherosclerosis. However, the signals that mediate this process are only partially understood. Prompted by putative links between inflammation and atherosclerosis, we previously reported that alpha-defensins released by neutrophils are present in human atherosclerotic lesions and promote the binding of lipoprotein(a) [Lp(a)] to vascular cells without a concomitant increase in degradation. We have now tested the hypothesis that this accumulation results from the propensity of defensin to form stable complexes with Lp(a) that divert the lipoprotein from its normal cellular degradative pathways to the extracellular matrix (ECM). In accord with this hypothesis, defensin stimulated the binding of Lp(a) to vascular matrices approximately 40-fold and binding of the reactants to the matrix was essentially irreversible. Defensin formed stable, multivalent complexes with Lp(a) and with its components, apoprotein (a) and low-density lipoprotein (LDL), as assessed by optical biosensor analysis, gel filtration, and immunoelectron microscopy. Binding of defensin/Lp(a) complexes to matrix was inhibited (>90%) by heparin and by antibodies to fibronectin (>70%), but not by antibodies to vitronectin or thrombospondin. Defensin increased the binding of Lp(a) (10 nmol/L) to purified fibronectin more than 30-fold. Whereas defensin and Lp(a) readily traversed the endothelial cell membranes individually, defensin/Lp(a) complexes lodged on the cell surface. These studies demonstrate that alpha-defensins released from activated or senescent neutrophils stimulate the binding of an atherogenic lipoprotein to the ECM of endothelial cells, a process that may contribute to lipoprotein accumulation in atherosclerotic lesions.


Defects in T-cell-mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector-mediated gene transfer into repopulating hematopoietic cells.
The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immune dysfunction, thrombocytopenia, and eczema. We used a murine model created by knockout of the WAS protein gene (WASP) to evaluate the potential of gene therapy for WAS. Lethally irradiated, male WASP- animals that received transplants of mixtures of wild type (WT) and WASP- bone marrow cells demonstrated enrichment of WT cells in the lymphoid and myeloid lineages with a progressive increase in the proportion of WT T-lymphoid and B-lymphoid cells. WASP- mice had a defective secondary T-cell response to influenza virus which was normalized in animals that received transplants of 35% or more WT cells. The WASP gene was inserted into WASP- bone marrow cells with a bicistronic oncoretroviral vector also encoding green fluorescent protein (GFP), followed by transplantation into irradiated male WASP- recipients. There was a selective advantage for gene-corrected cells in multiple lineages. Animals with higher proportions of GFP+ T cells showed normalization of their lymphocyte counts. Gene-corrected, blood T cells exhibited full and partial correction, respectively, of their defective proliferative and cytokine secretory responses to in vitro T-cell-receptor stimulation. The defective secondary T-cell response to influenza virus was also improved in gene-corrected animals.


Correlative Light-Electron Microscopy Shows RGD-Targeted ZnO Nanoparticles Dissolve in the Intracellular Environment of Triple Negative Breast Cancer Cells and Cause Apoptosis with Intratumor Heterogeneity.
ZnO nanoparticles (NPs) are reported to show a high degree of cancer cell selectivity with potential use in cancer imaging and therapy. Questions remain about the mode by which the ZnO NPs cause cell death, whether they exert an intra- or extracellular effect, and the resistance among different cancer cell types to ZnO NP exposure. The present study quantifies the variability between the cellular toxicity, dynamics of cellular uptake, and dissolution of bare and RGD (Arg-Gly-Asp)-targeted ZnO NPs by MDA-MB-231 cells. Compared to bare ZnO NPs, RGD-targeting of the ZnO NPs to integrin αvβ3 receptors expressed on MDA-MB-231 cells appears to increase the toxicity of the ZnO NPs to breast cancer cells at lower doses. Confocal microscopy of live MDA-MB-231 cells confirms uptake of both classes of ZnO NPs with a commensurate rise in intracellular Zn(2+) concentration prior to cell death. The response of the cells within the population to intracellular Zn(2+) is highly heterogeneous. In addition, the results emphasize the utility of dynamic and quantitative imaging in understanding cell uptake and processing of targeted therapeutic ZnO NPs at the cellular level by heterogeneous cancer cell populations, which can be crucial for the development of optimized treatment strategies.


Activism in an age of restraint: the resiliency of administrative structure in implementing the State Children's Health Insurance Program.
This article examines state efforts to build administrative structures and outreach networks in the State Children's Health Insurance Program (CHIP) through a comparative review of 18 states that have been the subject of ongoing research by the Nelson A. Rockefeller Institute of Government. The article explores the role that institutional structures play at the state level in shaping the implementation and administration of federal policy choices. States have generally opted to rely largely on existing Medicaid bureaucracies in order to implement the new CHIP programs. As a result, CHIP programs have been tightly integrated into existing Medicaid structures. Rarely put forward as exemplars of responsiveness and, these bureaucracies have nonetheless played a crucial role in building and managing CHIP programs across the United States. As this analysis will show, this has even been the case in those few states that have opted to officially house CHIP administration outside of the Medicaid bureaucracy. Furthermore, existing Medicaid systems have often been active as partners and participants in efforts to publicize and promote the CHIP program through outreach and education efforts. As part of these initiatives, efforts have been made to portray CHIP as a form of health insurance rather than a welfare benefit. A slight paradox results where key actors in the health and human services bureaucracy play an active role in program management while making efforts to dissassociate the program from the traditional welfare system. These efforts have been largely successful. And in doing so, not only have children been brought into the CHIP program but more families have been connected to the Medicaid program. In short, a review of state experiences reveals the resiliency and flexibility of existing state administrative systems in responding to and addressing substantive policy change.


Central Sensitisation and functioning in patients with chronic low back pain: protocol for a cross-sectional and cohort study.
A relevant subsample of patients with chronic low back pain (CLBP) have manifested augmented central pain processing, central sensitisation (CS). Patients with CLBP have limited functioning and participation. Theoretically, physical functioning in patients with CLBP can plausibly be linked to CS; however, evidence to explain such association is scarce. Moreover, there is no gold standard for CS diagnosis. The objectives of the study are: (1) to analyse the association between instruments assessing reference symptoms and signs attributed to CS; (2) to analyse whether reference symptoms and signs attributed to CS are associated with functioning measurement outcomes; and (3) to analyse whether changes (between baseline and discharge) in reference symptoms and signs attributed to CS are related to changes in each of the functioning measurement outcomes. A cross-sectional and longitudinal observational study is performed with measurements taken at baseline and discharge of an interdisciplinary rehabilitation programme. A sample size of 110 adult patients with CLBP has been calculated for the study. CS measurements are: Central Sensitisation Inventory, quantitative sensory testing and heart rate variability. Functioning measurements are: lifting capacity, maximal aerobic capacity, accelerometry and reported functioning. Statistical analyses to be performed are: (1) correlation between CS measurements, (2) multiple regression between functioning (dependent variable) and CS measurements (independent variable), and (3) multiple regression between changes in scores of functioning (dependent variable) and CS measurements (independent variable), and corrected for sex and age. The study obtained the clearance to its implementation from the Medical Research Ethics Committee of the University Medical Center Groningen in July 2017. The results will be disseminated through scientific publications in peer-reviewed journals, presentations at relevant conferences, and reports to stakeholders. NTR7167/NL6980.


Oral verrucous carcinoma: A retrospective analysis for clinicopathologic features.
To study the clinicopathological features of oral verrucous carcinoma (VC). Archives of the department were retrieved for verrucous lesions. After thorough histopathologic examination, 10 cases were confirmed as VC. Age, sex, site, tobacco habit, clinical presentation, and histologically, the presence of dysplasia and koilocytic changes were studied. Oral VC showed a distinct male preponderance with male:female ratio of 8:2 and occurring predominantly in sixth and seventh decade. Tobacco association in the form of chewing (50%), smoking (40%) or both (10%) was found in all the cases. In chewers, the site of lesion corresponded to the site of tobacco placement that is gingivobuccal sulcus. In smokers, the posterior part of the oral cavity was affected, and the lesions were extensive. Painless, exophytic, cauliflower-like growth was the most common presentation with surrounding whitish (leukoplakic) mucosa. Fifty percentage of the cases showed human papilloma virus-induced changes in the epithelium. Dysplasia was seen in two cases. Oral VCs are invariably associated with tobacco habits. In smokers, the lesions are extensive, affecting the posterior parts of the oral cavity. Although evidence of viral infection was seen but its role as an etiological agent is still controversial. Site and depth of the biopsy along with thorough histopathological sampling is essential to avoid erroneous diagnosis.


The cause of hepatic accumulation of fructose 1-phosphate on fructose loading.
1. The changes in the metabolite content in freeze-clamped livers of fed rats occurring on perfusion with 10mm-d-fructose have been examined. 2. The most striking effects of fructose were an accumulation of fructose 1-phosphate, as already known, up to 8.7mumol/g of liver within 10min, a loss of total adenine nucleotides (up to 35% after 40min) with a decrease in the ATP content to 23% within 10min, a sevenfold rise in the concentration of IMP to 1.1mumol/g and an eightfold rise of alpha-glycerophosphate to 1.1mumol/g. 3. There was a transient decrease in P(i) from 4.2 to 1.7mumol/g. Within 40min the P(i) content recovered to the normal value, probably because of an uptake of P(i) from the perfusion medium. 4. The degradation of the adenine nucleotides beyond the stage of AMP can be accounted for by the decrease of ATP and P(i). As ATP inhibits 5-nucleotidase, and as P(i) inhibits AMP deaminase any AMP arising in the tissue is liable to undergo dephosphorylation or deamination under the conditions occurring after fructose loading. 5. The content of lactate increased to 4.3mumol/g at 80min; pyruvate also increased and the [lactate]/[pyruvate] ratio remained within physiological limits. 6. The concentration of free fructose within the liver remained much below that in the perfusion medium, indicating that the rate of penetration of fructose into the tissue was lower than the rate of utilization. 7. The fission of fructose 1-phosphate by liver aldolase is inhibited by several phosphorylated intermediates, especially by IMP. This inhibition is competitive with a K(i) of 0.1mm. 8. The maximal rates of the enzymes synthesizing and splitting fructose 1-phosphate are about equal. The accumulation of fructose 1-phosphate on fructose loading is due to the inhibition of the fission of fructose 1-phosphate by the IMP arising from the degradation of the adenine nucleotides.


A pharmacoeconomic modeling approach to estimate a value-based price for new oncology drugs in Europe.
Several European governments have recently mandated price cuts in drugs to reduce health care spending. However, such measures without supportive evidence may compromise patient care because manufacturers may withdraw current products or not launch new agents. A value-based pricing scheme may be a better approach for determining a fair drug price and may be a medium for negotiations between the key stakeholders. To demonstrate this approach, pharmacoeconomic (PE) modeling was used from the Spanish health care system perspective to estimate a value-based price for bevacizumab, a drug that provides a 1.4-month survival benefit to patients with metastatic colorectal cancer (mCRC). The threshold used for economic value was three times the Spanish per capita GDP, as recommended by the World Health Organization (WHO). A PE model was developed to simulate outcomes in mCRC patients receiving chemotherapy ± bevacizumab. Clinical data were obtained from randomized trials and costs from a Spanish hospital. Utility estimates were determined by interviewing 24 Spanish oncology nurses and pharmacists. A price per dose of bevacizumab was then estimated using a target threshold of € 78,300 per quality-adjusted life year gained, which is three times the Spanish per capita GDP. For a 1.4-month survival benefit, a price of € 342 per dose would be considered cost effective from the Spanish public health care perspective. The price may be increased to € 733 or € 843 per dose if the drug were able to improve patient quality of life or enhance survival from 1.4 to 3 months. This study demonstrated that a value-based pricing approach using PE modeling and the WHO criteria for economic value is feasible and perhaps a better alternative to government mandated price cuts. The former approach would be a good starting point for opening dialog between European government payers and the pharmaceutical industry.


Long-term safety and effectiveness of high-dose dimethylfumarate in the treatment of moderate to severe psoriasis: a prospective single-blinded follow-up study.
Mixtures of fumaric acid esters (FAE) are used as an oral systemic treatment for moderate to severe psoriasis. Large clinical studies with dimethylfumarate (DMF) monotherapy are scarce. The objective of this study is to assess the effectiveness and long-term safety of high-dose DMF monotherapy in moderate to severe psoriasis. A prospective single-blinded follow-up study was performed in a cohort of patients treated with DMF. Patients were followed-up at fixed intervals. Assessment of consecutive photographs was performed by two observers. Primary outcome was a change in static physician global assessment (PGA) score. Safety outcome was defined as incidences of (serious) adverse events. A total of 176 patients with moderate to severe psoriasis were treated with DMF for a median duration of 28 months. The median daily maintenance dosage of 480 mg was reached after a median of 8 months. Psoriasis activity decreased significantly by 1.7 out of five points. A total of 152 patients reported one or more adverse events, such as gastrointestinal complaints and flushing. High-dose DMF monotherapy is an effective and safe treatment option in moderate to severe psoriasis. It can be suggested that 50% of all patients may benefit from high-dose DMF monotherapy.


Hepatocellular carcinoma. A worldwide problem and the major risk factors.
Male sex, age, cirrhosis, and HBsAg are the major risk factors for hepatocellular carcinoma (HCC). The geographic distribution of HCC is highly uneven, such that three distinct incidence areas are recognized. To clarify the reason(s) for this geographic variability of HCC, the risk factors in each incidence area were assessed. In parallel with the geographic distribution of HCC, HBsAg prevalence was highest in both HCC patients and in general population in Africa and Asia, where mothers of HCC patients are frequently HBsAg-positive, suggesting that hepatitis B virus hyperendemicity and perinatal infection account for the high HCC incidence in these areas. Cirrhosis, which is found on autopsy in 80% of the cases of HCC patients worldwide, is the most prevalent risk factor for HCC in areas where hepatitis B virus infection is less common. However, HBsAg carriage adds to the HCC risk carried by cirrhosis and explains the higher incidence of HCC in cirrhotics from Africa and Asia as well as elsewhere. Available data suggest that chronic HCV infection is a risk factor for cirrhosis and HCC. HBV vaccination should decrease HCC incidence rates worldwide; however, HCC prevention in regions where HBsAg carriage is infrequent may also require prevention of the other causes of cirrhosis in order for HCC rates to decline.


Building without a plan: the career experiences of Australian strength and conditioning coaches.
The purpose of this investigation was to explore the career experiences of Australian strength and conditioning coaches. Six Australian strength and conditioning coaches (mean age = 33.7 years, SD = 6.0 years) with a mean of 10.4 (SD = 4.9) years experience working with elite Olympic and professional athletes were interviewed about their experiences of career development. Each interview was transcribed verbatim and analyzed to produce key themes and subthemes relating to (a) work environments, (b) sport management practice, (c) career development processes, and (d) career building strategies. The work environments of Australian strength and conditioning coaches were found to be poor because of long working hours and irregular human resource policy and management practices of sport organizations. Because of the volatile and unpredictable nature of their working conditions, the coaches interviewed have only a short-term view of their career creating considerable stress in their lives. The coaches interviewed found it difficult to develop their careers because their only options were self-supported and self-funded professional development activities. The coaches in this study believed that more needed to be done at a policy and management level by sport organizations and their professional body to enhance the career development of strength and conditioning coaches because they play a key role in both athlete and sport organization performance. These results may help sport organizations develop policies and management practices that enhance the careers of strength and conditioning coaches and will have important practical implications for the education and development of sport professionals.


Differential role of long terminal repeat control elements for the regulation of basal and Tat-mediated transcription of the human immunodeficiency virus in stimulated and unstimulated primary human macrophages.
Primary human macrophages induced to differentiate through contact with autologous activated nonadherent cells were used to investigate the transcriptional mechanisms involved in reactivation of human immunodeficiency virus (HIV) replication. Through transient transfection experiments with an HIV long terminal repeat (LTR)-chloramphenicol acetyltransferase reporter construct, we show that macrophage differentiation results in a 20-fold upregulation of basal LTR activity. To identify sequence elements responsive to the differentiation process, point mutations introduced into the LTR were tested in differentiated and undifferentiated macrophages. Several elements were identified as positive regulators of basal transcription. TATA, Sp1, and NF-kappa B binding sites were the most influential. The low-affinity site for LBP-1 (UBP-1) functioned as a negative regulator of LTR activity in undifferentiated macrophages, but this influence was lost upon differentiation. When tat was cotransfected into the expression system, the requirement for LTR elements identified as important for positive regulation of basal transcription remained in undifferentiated macrophages. Interestingly, however, the mutations in positive control elements which debilitated activity in undifferentiated macrophages had no effect on LTR activity in differentiated macrophages. Thus, it appears that while HIV-LTR activity is highly dependent on cellular transcription factors in undifferentiated cells, in differentiated macrophages the viral protein Tat confers pliability on the LTR and facilitates autonomy from absolute cellular control mechanisms. In vivo, release from either positive or negative regulation via cellular proteins may facilitate reactivation of HIV in macrophages.


Density wave propagation of a wave train in a closed excitable medium.
A wave train in an excitable reaction-diffusion medium shows a variety of spatiotemporal patterns as a result of interactions between the individual waves. In this paper, we report a novel spatiotemporal pattern in a wave train in a closed excitable medium. We carried out experiments using a photosensitive Belousov-Zhabotinsky reaction with Ru(bpy)(3)(2+) as a catalyst and a numerical calculation using the FitzHugh-Nagumo equation. A wave train was locally distributed as an initial condition and the number of waves was systematically varied. In both the experiment and numerical calculation, density wave propagation was formed in a wave train during relaxation with a large number of waves. Our results suggest that density wave propagation originates from inhibitory interaction between the waves.


Association of vascular endothelial growth factor a gene (VEGFA) polymorphisms, rs699947 and rs1570360, with diabetic retinopathy and altered VEGF secretion in the Pakistani patients with type 2 diabetes mellitus: a casecontrol study.
To investigate the association of vascular endothelial growth factor A gene polymorphisms 2578C/A (rs699947) and 1154G/A (rs1570360) with type 2 diabetes mellitus, diabetic retinopathy and serum vascular endothelial growth factor levels in Pakistani patients. The case-control study was conducted from Jan 2017 to Dec 2018 after approval from the ethics review board of Riphah International University, Islamabad, Pakistan, and comprised type 2 diabetes mellitus patients of either gender with diabetic retinopathy in group A, and without diabetic retinopathy in group B. Non-diabetic healthy individuals were enrolled in control group C. Genotyping was done by amplification refractory mutation system-polymerase chain reaction and serum vascular endothelial growth factor levels were measured using enzyme-linked immunosorbent assay. Data was analysed using SPSS 22. Of the 450 subjects, 150(33.3%) were in each of the 3 groups. The mean age in group A was 58.16±9.42, in group B 56.25±8.5 years and in group C it was 55.90±10.90. The proportion of Punjabi ethnicity was significantly high in group B compared to other groups (p<0.05). There was no significant association of rs699947 and rs1570360 genotypic and allelic frequencies in group B compared to group A. Further, rs699947 AA genotype was significantly associated with proliferative diabetic retinopathy compared to group A (p<0.05). Minor allele A showed significant association in groups A and B compared to group C (p<0.05). Significantly raised serum vascular endothelial growth factor levels were found in group B compared to group A (p<0.05), and were associated with rs699947 and rs1570360 heterozygosity in group A (p<0.05). Also, rs699947 genotype showed significant association with groups A and B in Punjabi and Pathan ethnicities (p<0.05) and with Kashmiri ethnicity in group B (p<0.05). There was a strong association of vascular endothelial growth factor 2578C/A (rs699947) gene polymorphism with proliferative diabetic retinopathy in type 2 diabetic Pakistani patients, suggesting its role in the pathogenesis of this condition.


Why do shrews twitter? Communication or simple echo-based orientation.
Shrews are very vocal animals. We tested behaviourally whether the high-pitched laryngeal 'twittering' calls of as-yet unclear function serve for communication or echo-based orientation. We used a representative species from each of the two largest phylogenetic groups of shrews. In both species, experimental manipulation of substrate density, but not of the likelihood of conspecific presence, affected the shrews' call rate when exploring an unknown environment. This adaptation of call rate to the degree of habitat clutter parallels bat echolocation and suggests that shrews may use the echoes and reverberations of their calls for identifying routes through their habitat or for probing habitat type. To assess the acoustic feasibility of shrew echo orientation, we ensonified shrew habitats in the field with an 'artificial shrew' (small speaker mounted close to a sensitive microphone). The data showed that shrew-like calls can indeed yield echo scenes useful for habitat assessment at close range, but beyond the range of the shrews' vibrissae.


Cardiovascular disease and arterial calcification in insulin-dependent diabetes mellitus: interrelations and risk factor profiles. Pittsburgh Epidemiology of Diabetes Complications Study-V.
Cardiovascular disease is a frequent complication of insulin-dependent diabetes mellitus (IDDM), but the prevalence, interrelations, and risk factors of its principal components (coronary, cerebrovascular, and lower-extremity arterial disease) and of medial arterial wall calcification are not well understood. To address these issues, data from the Epidemiology of Diabetes Complications Study (n = 657) baseline examination were examined. The term coronary heart disease (CHD) was applied to those with myocardial infarction or angina, whereas lower-extremity arterial disease (LEAD) was applied to those who had undergone amputation of a lower limb or who had an ankle to arm blood pressure ratio less than 0.8 at rest or after exercise. Calcification of the lower-extremity arteries was considered to be present if ankle pressure was more than 100 mm Hg higher than brachial pressure. Although the prevalence of CHD was low, LEAD was significantly more common in women than in men (p less than 0.01), whereas calcification was more frequent in men than in women (p less than 0.01). Ten percent of those with LEAD also had CHD, and 8% with LEAD had calcification. Modeling of potential risk factors (e.g., diabetes duration and glycosylated hemoglobin) revealed that duration, female gender, fibrinogen, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and high density lipoprotein cholesterol to apolipoprotein A-I ratio were independent predictors of LEAD, whereas for CHD only, diabetes duration and hypertension contributed to CHD. Calcification revealed a mixed pattern, with duration, hypertension, and triglyceride to apolipoprotein A-I ratio being the statistically significant associated factors. The results suggest that although LEAD, CHD, and calcification often coexist, their risk factor profiles differ.


[Clinical reasoning and decision-making in practice. A man with swelling of both corners of the jaw].
A 33-year-old man was referred to an oral surgeon by his general practitioner because ofa bilateral swelling in both jaws. A CT-scan of the head showed enlargement of the parotid glands. After exclusion of mumps and sialolithiasis the patient was treated with oral antibiotics. The swelling failed to improve and the patient was sent to an internist. A repeated medical history revealed that he also had symptoms of sicca syndrome. Sjögren's syndrome was excluded only after negative immunoserological tests and sublabial salivary gland biopsy. A chest X-ray showed enlarged bilateral hilar lymph nodes, confirming the diagnosis of sarcoidosis. A gallium scintigraphy provided further support for this diagnosis. No treatment was initiated and the patient recovered slowly afterwards.


Ultrastructural and molecular confirmation of the development of Sarcocystis neurona tissue cysts in the central nervous system of southern sea otters (Enhydra lutris nereis).
In 2004, three wild sea otters were diagnosed with putative Sarcocystis neurona-associated meningoencephalitis by histopathology and immunohistochemistry. Schizonts, free merozoites and tissue cysts were observed in the brains of all three infected animals. Tissue cysts walls from sea otter 1 (SO1) stained positively using anti-S. neurona polyclonal antiserum. However, positive staining does not preclude infection by closely related or cross-reactive tissue cyst-forming coccidian parasites. Two immature tissue cysts in the brain of SO1 were examined using transmission electron microscopy. Ultrastructural features included cyst walls with thin villous projections up to 1 microm long with tapered ends and a distinctive, electron-dense outer lining layer composed of linearly-arranged, semi-circular structures with a "hobnailed" surface contour. Small numbers of microtubules extended down through the villi into the underlying granular layer. Metrocytes were short and plump with an anterior apical complex, 22 sub-pellicular microtubules, numerous free ribosomes and no rhoptries. Some metrocytes appeared to be dividing, with two adjacent nuclear profiles. Collectively these ultrastructural features were compatible with developing protozoal cysts and were similar to prior descriptions of S. neurona tissue cysts. Panspecific 18S rDNA primers were utilized to identify protozoa infecting the brains of these otters and DNA amplification and additional sequencing at the ITS1 locus confirmed that all three otters were infected with S. neurona. No other Sarcocystis spp. were detected in the brains or skeletal muscles of these animals by immunohistochemistry or PCR. We believe this is the first ultrastructural and molecular confirmation of the development of S. neurona tissue cysts in the CNS of any animal.


Impact of a workplace intervention on attitudes and practices related to gender equity in Bengaluru, India.
We describe the evaluation of a participatory, garment factory-based intervention to promote gender equity. The intervention comprised four campaigns focused on gender and violence against women, alcoholism, sexual and reproductive health, and HIV/AIDS, which were implemented using information displays (standees and posters) and interactive methods (street play, one-to-one interactions, experience-sharing, and health camps). Each campaign lasted six days and the entire intervention was implemented over 10 months. We evaluated the intervention using a quasi-experimental design in which one factory served as the intervention site and a second as a delayed control. Two mobile-phone-based cross-sectional surveys were conducted at baseline and 12 months with separate systematic random samples of employees from each site. Data on socio-demographic characteristics and knowledge and attitudes related to gender equity, intimate partner violence (IPV) and alcohol use were assessed, and differences in these variables associated with the intervention were examined using difference-in-difference estimation. Analyses of data from 835 respondents revealed substantial, statistically significant improvements in attitudes related to gender equity, unacceptability of IPV, and awareness of IPV and alcohol-related support services. In conclusion, our study offers compelling evidence on the effectiveness of workplace-based interventions in advancing gender equity.


[Foreign and self--the challenge for the immune system].
This process of thymic selection produces a repertoire of T-cells able to recognize foreign antigens but to remain nonreactive to the body's own antigens, designated "self" (central tolerance). The interaction between lymphoid and stromal cells within the thymic microenvironment is critical in order to shape the correct antigen specificity of the T-cell repertoire. The thymus has been regarded as the main site of tolerance induction to ubiquitous self-antigens, i.e. abundant blood-borne self-antigens or proteins that are expressed by thymic cells. In contrast, tolerance to ubiquitous, i.e. tissue-restricted, self-antigens has been attributed to extrathymic, peripheral mechanisms. Here I review scientific evidence which assigns a much larger role for the thymus in tissue-specific tolerance. The reason for this paradigmatic shift is, first, the discovery of ectopic expression of tissue-restricted self-antigens by thymic medullary epithelial cells (TECs) which thus present to developing T-cells a "molecular mirror of peripheral self". As a consequence, central tolerance to many peripheral self-antigens can be generated. Second, the thymus is capable to produce regulatory T-cells. Such CD4+CD25+Foxp3+ T-cells are selected by antigens presented by medullary TECs and can control in the periphery the activation of tissue-specific self-reactive T-cells by use of active inhibitory mechanisms. These new insights have implications for our understanding of self-tolerance and its breakdown in autoimmune diseases.


An Evolutionary Insight into Zika Virus Strains Isolated in the Latin American Region.
Zika virus (ZIKV) is an emerging pathogen member of the Flaviviridae family. ZIKV has spread rapidly in the Latin American region, causing hundreds of thousands of cases of ZIKV disease, as well as microcephaly in congenital infections. Detailed studies on the pattern of evolution of ZIKV strains have been extremely important to our understanding of viral survival, fitness, and evasion of the host's immune system. For these reasons, we performed a comprehensive phylogenetic analysis of ZIKV strains recently isolated in the Americas. The results of these studies revealed evidence of diversification of ZIKV strains circulating in the Latin American region into at least five different genetic clusters. This diversification was also reflected in the different trends in dinucleotide bias and codon usage variation. Amino acid substitutions were found in E and prM proteins of the ZIKV strains isolated in this region, revealing the presence of novel genetic variants circulating in Latin America.


Sensitive determination of D-amino acids in mammals and the effect of D-amino-acid oxidase activity on their amounts.
The determination of small amounts of D-amino acids in mammalian tissues is still a challenging theme in the separation sciences. In this review, various gas-chromatographic and high-performance liquid chromatographic methods are discussed including highly selective and sensitive column-switching procedures. Based on these methods, the distributions of D-aspartic acid, D-serine, D-alanine, D-leucine and D-proline have been clarified in the mouse brain. As the regulation mechanisms of D-amino acid amounts in mammals, we focused on the D-amino-acid oxidase, which catalyzes the degradation of D-amino acids. Using the mutant mouse strain lacking D-amino-acid oxidase activity, the effects of the enzymatic activity on the amounts and distributions of various D-amino acids have been investigated.


Genetics and alcoholism among at-risk relatives I: perceptions of cause, risk, and control.
Genetic factors influence a person's risk for developing alcoholism. In other common disorders with a genetic component, a belief in a genetic cause can lead to less perceived control or fatalism among those at risk that may adversely affect undertaking health-promoting behaviors. This study explores beliefs about the cause of alcoholism and risk perception among individuals with affected relatives. In-depth interviews including both open-ended questions and several quantitative measures were conducted with participants to explore the relationships between causal beliefs and perceptions of personal risk and control. Twenty-seven individuals with at least one first-degree relative affected with alcoholism participated. Transcript analysis of interviews revealed that all participants attribute multiple factors to the cause of alcoholism in their families, often as a combination of biological, genetic, environmental factors, and personal characteristics. Many perceived themselves as being 'at-risk,' and this concern often stemmed from a belief in a genetic or biological cause of alcoholism. However, participants also had a strong sense of personal control, rooted in beliefs about environmental causes or personal characteristics influencing alcoholism risk. A participant's strong belief in a genetic cause was associated with a significantly increased risk perception, but not a fatalistic outlook towards developing alcoholism.


SIRT5 is a proviral factor that interacts with SARS-CoV-2 Nsp14 protein.
SARS-CoV-2 non-structural protein Nsp14 is a highly conserved enzyme necessary for viral replication. Nsp14 forms a stable complex with non-structural protein Nsp10 and exhibits exoribonuclease and N7-methyltransferase activities. Protein-interactome studies identified human sirtuin 5 (SIRT5) as a putative binding partner of Nsp14. SIRT5 is an NAD-dependent protein deacylase critical for cellular metabolism that removes succinyl and malonyl groups from lysine residues. Here we investigated the nature of this interaction and the role of SIRT5 during SARS-CoV-2 infection. We showed that SIRT5 stably interacts with Nsp14, but not with Nsp10, suggesting that SIRT5 and Nsp10 are parts of separate complexes. We found that SIRT5 catalytic domain is necessary for the interaction with Nsp14, but that Nsp14 does not appear to be directly deacylated by SIRT5. Furthermore, knock-out of SIRT5 or treatment with specific SIRT5 inhibitors reduced SARS-CoV-2 viral levels in cell-culture experiments. SIRT5 knock-out cells expressed higher basal levels of innate immunity markers and mounted a stronger antiviral response. Our results indicate that SIRT5 is a proviral factor necessary for efficient viral replication, which opens novel avenues for therapeutic interventions.


Influence of copigment derived from Tasmannia pepper leaf on Davidson's plum anthocyanins.
Davidson's plum (Davidsonia pruriens, F. Muell.), a native to Australian rainforests, large, crimson-red fruit, which superficially resembles plum, has been commercially cultivated in Australia since 1990s. The current production volume exceeds market demands therefore this study was designed to evaluate the suitability of Davidson's plum extract as a source of anthocyanin-based food colorant. The stability of the Davidson's plum extract towards heat treatment at 95 °C was higher than that of commercial mulberry colorant, but inferior to colorants derived from red cabbage and purple sweetpotato. An addition of a variety of phenolic acids significantly increased color intensity indicating the formation of copigmentation complexes. Commercial chlorogenic acid as well as extract from a native Australian herb rich in chlorogenic acid, Tasmannia pepper leaf (Tasmannia lanceolata, R. Br.), were both tested in model soft drink solutions subjected to light irradiation and heat treatment. In both cases, the addition of the copigment resulted in a lasting increase in color intensity. In conclusion, Davidson's plum extract can successfully be utilized as a source of natural food color. Extract from Tasmania pepper leaf can be used as a co-pigment for Davidson's plum anthocyanins. The color properties of an anthocyanin colorant derived from the native Australian fruit Davidson's plum are comparable to those of mulberry, which is currently applied as a food colorant in Australian food products. Utilization of Davidson's plum fruit as a source of natural color will allow the industry to increase the range of natural pigments and will create new opportunities for the emerging native food industry.


Fetal testosterone and autistic traits.
Studies of amniotic testosterone in humans suggest that fetal testosterone (fT) is related to specific (but not all) sexually dimorphic aspects of cognition and behaviour. It has also been suggested that autism may be an extreme manifestation of some male-typical traits, both in terms of cognition and neuroanatomy. In this paper, we examine the possibility of a link between autistic traits and fT levels measured in amniotic fluid during routine amniocentesis. Two instruments measuring number of autistic traits (the Childhood Autism Spectrum Test (CAST) and the Child Autism Spectrum Quotient (AQ-Child)) were completed by these women about their children (N=235), ages 6-10 years. Intelligence Quotient (IQ) was measured in a subset of these children (N=74). fT levels were positively associated with higher scores on the CAST and AQ-Child. This relationship was seen within sex as well as when the sexes were combined, suggesting this is an effect of fT rather than of sex per se. No relationships were found between overall IQ and the predictor variables, or between IQ and CAST or AQ-Child. These findings are consistent with the hypothesis that prenatal androgen exposure is related to children exhibiting more autistic traits. These results need to be followed up in a much larger sample to test if clinical cases of ASC have elevated fT.


[Chronic rubella virus-induced infection of human continuous cells].
A stable chronically rubella virus-infected culture of HEp-2-BK cells existing for over 30 months has been obtained as a result of a single inoculation and further passages. This system is characterized by the lack of cell destruction and permanent production of infectious virus in titres of 2.5-6.3 lg PFU/ml. Synthesis of RNAs of the same classes as in the acute infection was demonstrated in the chronically infected cell culture (CICC) but virion RNA production was less marked. Only a portion of the cells in the population was found to carry the infectious virus. Virus-free cell clones were as susceptible to rubella virus as the control culture. The process of persistence proved to be resistant to virus-specific antibody as well as to the effect of higher (40 degree C) or lower (34 degree C) temperatures. Actinomycin D, 5-bromodeoxyuridine, and 5-iodo-2-deoxyuridine exerted no significant effect on virus reproduction in CICC which, combined with negative results of the experiments on transfection of the susceptible cultures with DNA preparations recovered from CICC, evidenced against the role of integration mechanisms in the establishment and maintenance of the HEp-2-BK system. A clear-cut interference with a heterologous virus was demonstrated in HEp-2-BK culture. The formation of the chronic form of infection in HEp-2-BK culture appears to be due to weak cytocidal properties of rubella virus and formation of endogenous interferon.


Statics and dynamics of polymeric droplets on chemically homogeneous and heterogeneous substrates.
We present a molecular dynamics study of the motion of cylindrical polymer droplets on striped surfaces. We first consider the equilibrium properties of droplets on different surfaces, we show that for small stripes the Cassie-Baxter equation gives a good approximation of the equilibrium contact angle. As the stripe width becomes nonnegligible compared to the dimension of the droplet, it has to deform significantly to minimize its free energy; this results in a smaller value of the contact angle than the continuum model predicts. We then evaluate the slip length and thus the damping coefficient as a function of the stripe width. For very small stripes, the heterogeneous surface behaves as an effective surface, with the same damping as a homogeneous surface with the same contact angle. However, as the stripe width increases, damping at the surface increases until reaching a plateau. Afterwards, we study the dynamics of droplets under a bulk force. We show that if the stripes are large enough the droplets are pinned until a critical force. The critical force increases linearly with stripe width. For large enough forces, the average velocity increases linearly with the force, we show that it can then be predicted by a model depending only on droplet size, contact angle, viscosity, and slip length. We show that the velocity of the droplet varies sinusoidally as a function of its position on the substrate. However, for bulk forces just above the depinning force we observe a characteristic stick-slip motion, with successive pinnings and depinnings.


GPS-based fine-scale mapping surveys for schistosomiasis assessment: a practical introduction and documentation of field implementation.
Fine-scale mapping of schistosomiasis to guide micro-targeting of interventions will gain importance in elimination settings, where the heterogeneity of transmission is often pronounced. Novel mobile applications offer new opportunities for disease mapping. We provide a practical introduction and documentation of the strengths and shortcomings of GPS-based household identification and participant recruitment using tablet-based applications for fine-scale schistosomiasis mapping at sub-district level in a remote area in Pemba, Tanzania. A community-based household survey for urogenital schistosomiasis assessment was conducted from November 2020 until February 2021 in 20 small administrative areas in Pemba. For the survey, 1400 housing structures were prospectively and randomly selected from shapefile data. To identify pre-selected structures and collect survey-related data, field enumerators searched for the houses' geolocation using the mobile applications Open Data Kit (ODK) and MAPS.ME. The number of inhabited and uninhabited structures, the median distance between the pre-selected and recorded locations, and the dropout rates due to non-participation or non-submission of urine samples of sufficient volume for schistosomiasis testing was assessed. Among the 1400 randomly selected housing structures, 1396 (99.7%) were identified by the enumerators. The median distance between the pre-selected and recorded structures was 5.4 m. A total of 1098 (78.7%) were residential houses. Among them, 99 (9.0%) were dropped due to continuous absence of residents and 40 (3.6%) households refused to participate. In 797 (83.1%) among the 959 participating households, all eligible household members or all but one provided a urine sample of sufficient volume. The fine-scale mapping approach using a combination of ODK and an offline navigation application installed on tablet computers allows a very precise identification of housing structures. Dropouts due to non-residential housing structures, absence, non-participation and lack of urine need to be considered in survey designs. Our findings can guide the planning and implementation of future household-based mapping or longitudinal surveys and thus support micro-targeting and follow-up of interventions for schistosomiasis control and elimination in remote areas. Trial registration ISRCTN, ISCRCTN91431493. Registered 11 February 2020, https://www.isrctn.com/ISRCTN91431493.


Transgressing the ventricular wall during subthalamic deep brain stimulation surgery for Parkinson disease increases the risk of adverse neurological sequelae.
Deep brain stimulation (DBS) at the subthalamic nucleus (STN) is an effective treatment for the motor manifestations of advanced medically refractory Parkinson disease. Because of the medial location of the target, surgical trajectories to the STN may violate the ipsilateral lateral ventricle. To determine whether violating the ventricle during STN DBS surgery is associated with postoperative confusion. A retrospective chart review of all STN implantation procedures for Parkinson disease performed by 1 surgeon between January 2005 and September 2008 was performed. Postoperative magnetic resonance imaging was performed in all cases, and each scan was reviewed for evidence of ventricular wall violation. All charts were reviewed for postoperative confusion and/or increased length of hospital stay. A total of 145 leads were implanted in 81 patients over 102 admissions. Forty-three patients underwent contemporaneous bilateral lead implantation; 23 underwent unilateral implantation; and 18 underwent staged bilateral implantation. The cases of 8 patients were complicated by postoperative confusion and increased length of stay. Sixteen magnetic resonance imaging scans demonstrated evidence of ventricular wall violation including all 8 patients with postoperative confusion. The relative risk of having postoperative confusion after traversing the ventricle is 87 (P < .001). Violating the ventricular system during STN DBS surgery correlated significantly with postoperative altered mental status and subsequent increased length of hospital stay. This finding may explain why cognitive complications are observed more frequently in Parkinson disease patients undergoing DBS at the STN compared with the internal globus pallidus.


Approach to ovarian torsion with corpus luteum re-moval in early pregnancy.
The ovary's Torsion is the adnexa's total or partial rotation around its vascular axis or pedicle. Complete torsion causes venous and lymphatic blockade leading to stasis, venous congestion, hemorrhage, and necrosis. If neglected, it may result in permanent loss of the affected ovary. Ovarian torsion is one of the most critical gynecological surgical emergencies. Therefore, it requires urgent surgical intervention. It is mainly diagnosed by clinical examination and ultrasound. Ovarian torsion is primarily seen in the first trimester of pregnancy.1,2 Infertility treatment is a significant risk factor due to ovarian stimulation. We present a case of acute abdominal pain who came to the emergency department of Al Ahli Hospital, diagnosed as right adnexal torsion with viable intrauterine pregnancy at six weeks. Laparoscopic oophorectomy was done by removing the corpus luteum cyst, which supports early pregnancy. Despite its disposal, the pregnancy continued because the hormonal therapy started in doses higher than recommended for threatened abortion.3 Eventually, she gave birth to a healthy baby boy at 35 weeks.


Histomorphometrics and quantitative unbiased stereology in canine uteri treated with medroxyprogesterone acetate.
This article describes the effects of MPA use on the canine uterus using stereological methods. Entire reproductive tracts were removed from normal healthy canine bitches (Canis lupus familiaris) and grouped as: nulliparous (n = 11), multiparous (n = 11) and MPA-treated (n = 11; nulliparous; two treatments; 5 mg/kg). 1 cm samples were cut from the corpus, horn and uterine tube and fixed in 10% formaldehyde. Sections of each were mounted on slides and stained with hematoxylin-eosin. We assessed the fraction area for components of endometrium and myometrium and VV (volume density) and SV (surface density) of the gland and stroma using the M36 test system provided by the STEPanizer Stereological Tool. No gross histological differences were observed between study groups in the uterine tube, uterine corpus and horn. The wall of the uterine corpus and horn in MPA-treated bitches was characterized as being thicker than in the other groups. A cross-section of the uterine corpus revealed no differences between components of uterine wall in the corpus and horn; however, differences were observed in the volume density [VV; %] in variables such as: VV[str.vasc/uterus] (nulliparous vs. multiparous; p = 0.0019) and VV[str.supravasc/uterus] (multiparous vs. nulliparous and MPA; p = 0.0035). In the endometrial gland, differences were detected in SV[gland/endom] (multiparous vs. MPA, p = 0.0442). In the uterine horn, differences were only observed in the variable VV[lumen.gland/endom] (multiparous vs. MPA; p = 0.0019). This study shows quantitative changes in the architecture of the endometrium and myometrium in all the uterine segments, mainly morphological endometrial gland changes of the uterine corpus, increasing the surface area per unit of volume; however, these changes usually do not differ quantitatively from those observed in the uterus of multiparous bitches.


Stereotypes and steroids: using a psychobiosocial model to understand cognitive sex differences.
To further our understanding of cognitive sex differences, we studied the relationship between menstrual phase (via serum estradiol and progesterone levels) and cognitive abilities and cognitive performance in a sample of medical students in eastern Turkey. As expected, we found no sex differences on the Cattell "Culture Fair Intelligence Test" (a figural reasoning test), with females scoring significantly higher on a Turkish version of the Finding A's Test (rapid word knowledge) and males scoring significantly higher on a paper-and-pencil mental rotation test. The women showed a slight enhancement on the Finding A's Test and a slight decrement in Cattell scores during the preovulatory phase of their cycle that (probably) coincided with a rise in estrogen. There were also small cycle-related enhancements in performance for these women on the mental rotation test that may reflect cyclical increases in estrogen and progesterone. Additional analyses showed an inverted U-shaped function in level of estradiol and the Cattell Test. Finally, for women who were tested on Day 10 of their menstrual cycle, there was a negative linear relationship between their Cattell scores and level of progesterone. Stereotypes about the cognitive abilities of males and females did not correspond to performance on the mental rotation or Finding A's Test, so the sex-typical results could not be attributed to either stereotype threat or stereotype activation. For practical purposes, hormone-related effects were generally small. Variations over the menstrual cycle do not provide evidence for a "smarter" sex, but they do further our understanding of steroidal action on human cognitive performance.


The study of reinnervation of gastric vagus nerves after lesser curvature and fundus myotomy in cats.
The aim of this study was to investigate the reinnervation of gastric vagus nerves after lesser curvature and fundus myotomy (LCFM) in cats. After injection of the retrogradely tracing agent horseradish peroxidase (HRP) into the stomach wall along the predicted line of LCFM, the neuronal cell bodies of the afferent and efferent fibers were well-defined in both the nodose ganglia (NG) and dorsal motor nucleus of the vagus nerve (DMNx), respectively. The animals were divided into three subgroups. After LCFM, at intervals of 0 day, 2, 4, 6, 8, 10 and 12 weeks, respectively, they were processed for a HRP histochemical study in both subgroups A and B. In subgroup A, HRP was directly injected into both sides of the stomach wall distal to the dissecting plane of LCFM. A further corpoantral circumferential myotomy (CACM) was performed in subgroup B to eliminate the possibility of collateral sprouting via antropyloric vagus innervation before applying HRP to the same sites as those of subgroup A. Both LCFM and CACM with an overlapping suture were performed in subgroup C, and HRP was then injected into sites similar to those of subgroup A on the twelfth postoperative week. HRP-labeled cells were found in the NG on the sixth week and in the DMNx on the eighth week in subgroups A and B. The labeled cells increased in number until the twelfth week in both subgroups A and B. However, cells found in subgroup A were always more numerous than those found in subgroup B in both the NG and DMNx at equivalent time intervals. No labeled cell was found in the NG or DMNx in subgroup C during the 12 week study period.(ABSTRACT TRUNCATED AT 250 WORDS)


[Keratoplasty in children and juveniles].
The morphological and functional results of 42 penetrating keratoplasties performed on 38 eyes of 36 children are reported on. Surgical indications, contraindications and postoperative complications are discussed. Emphasis is placed on the close cooperation between the clinic, the practitioner responsible for the aftercare, and the parents of the child.


Low-frequency heart rate variability is related to the breath-to-breath variability in the respiratory pattern.
Changes in heart rate variability (HRV) at "respiratory" frequencies (0.15-0.5 Hz) may result from changes in respiration rather than autonomic control. We now investigate if the differences in HRV power in the low-frequency (LF) band (0.05-0.15 Hz, HRV(LF)) can also be predicted by respiration variability, quantified by the fraction of tidal volume power in the LF (V(LF,n)). Three experimental protocols were considered: paced breathing, mental effort tasks, and a repeated attentional task. Significant intra- and interindividual correlations were found between changes in HRV(LF) and V(LF,n) despite all subjects having a respiratory frequency above the LF band. Respiratory parameters (respiratory period, tidal volume, and V(LF,n)) could predict up to 79% of HRV(LF) differences in some cases. This suggests that respiratory variability is another mechanism of HRV(LF) generation, which should be always monitored, assessed, and considered in the interpretation of HRV changes.


Effects of Cold Therapy on Pain and Anxiety During Needle Removal From Implanted Ports.
This study was conducted as a quasiexperimental, single-blind study to examine the effect of cold therapy on pain and anxiety during port needle removal. Patients in the experimental group received cold therapy 10 minutes before port needle removal. Patients in the control group received no intervention before port needle removal. Data were collected using the visual analog scale (VAS) and State-Trait Anxiety Inventory (STAI). After cold therapy was applied to the patients in the experimental group, the second and third VAS scores were found to be statistically significant and lower than those in the control group ( P < .05). There was no statistically significant difference between the anxiety levels of the experimental group and the control group before cold therapy ( P > .005). However, the STAI scores of the experimental group were found to be statistically and significantly lower than those of the control group after cold therapy ( P < .05). This study determined that cold therapy before port needle removal reduces pain and anxiety. Cold therapy may be recommended as an effective nonpharmacological pain control method with ease of application to prevent pain induced by port needle removal.


Isolation of multiple drug-resistant enteric bacteria from feces of wild Western Lowland Gorilla (Gorilla gorilla gorilla) in Gabon.
Prevalence of drug-resistant bacteria in wildlife can reveal the actual level of anthropological burden on the wildlife. In this study, we isolated two multiple drug-resistant strains, GG6-2 and GG6-1-1, from 27 fresh feces of wild western lowland gorillas in Moukalaba-Doudou National Park, Gabon. Isolates were identified as Achromobacter xylosoxidans and Providencia sp., respectively. Minimum inhibitory concentrations of the following 12 drugs-ampicillin (ABPC), cefazolin (CEZ), cefotaxime (CTX), streptomycin (SM), gentamicin (GM), kanamycin (KM), tetracycline (TC), nalidixic acid (NA), ciprofloxacin (CPFX), colistin (CL), chloramphenicol (CP) and trimethoprim (TMP)-were determined. Isolate GG6-2 was resistant to all antimicrobials tested and highly resistant to CTX, SM, TC, NA and TMP. Isolate GG6-1-1 was resistant to ABPC, CEZ, TC, CL, CP and TMP.


Raloxifene therapy inhibits osteoclastogenesis during the alveolar healing process in rats.
To investigate the expression of OPG, RANKL and TRAP during alveolar healing process (7, 14, 21, 28 and 42 postoperative days) in ovariectomized rats treated with raloxifene or with oestrogen replacement therapy, using immunohistochemistry reaction approach. Wistar female rats (10 weeks age) were submitted to ovariectomy surgery (OVX) or sham surgery. The female rats were divided in four groups: (1) sham; (2) OVX/O (ovariectomy and oil); (3) OVX/E2 (ovariectomy and oestrogen replacement); (4) OVX/RLX (ovariectomy and raloxifene therapy). It was observed high amount of OPG immunolabelling with predominance at 14 and 21 postoperative days on sham and OVX/RLX groups, respectively. At 7 postoperative days, there was no difference between the groups for TRAP protein. Otherwise, to the other periods, it was observed greater expression of TRAP and RANKL protein on OVX/O group compared to sham, OVX/E2 and OVX/RLX groups. It was also observed a discrete TRAP immunolabelling at 28 and 42 postoperative days on OVX/RLX group. Oestrogen deficiency induces osteoclastogenesis in the alveolar healing process. Quantitative changes in the osteoclastic activity could be prevented through the raloxifene therapy.