Blood content of broiler chicken carcases prepared by different slaughter methods.
Two trials using broiler chickens were undertaken to determine if variations in commercial slaughter techniques affected either the appearance or the residual blood content of the carcases produced. In the first trial groups of broilers were either stunned (55, 80 or 105 volts), electrocuted (240 volts) or anaesthetised and the subsequent bleed-out volumes after one, two, three and four minutes exsanguination were measured. The method of slaughter made no difference to the amount of blood lost after venesection. Haemoglobin content of the pectoral muscle was used to measure residual blood and was uniformly low in all groups (0.7 to 0.16 mg haemoglobin/g of muscle). In the second trial groups of chickens were either stunned and bled out, electrocuted, electrocuted and bled out, decapitated or halal killed before processing. The edible portions of the carcases were minced and the average haemoglobin content for each group was 0.19, 0.36, 0.22, 0.17 and 0.17 mg/g of soft tissue. The appearance of chickens that were stunned and bled out was the same as that of chickens that were electrocuted and bled out. The authors conclude that killing chickens by electrocution before exsanguination does not adversely affect the carcase appearance. Furthermore, electrocution ensures that broiler chickens are humanely slaughtered.


Analysis of diepoxide-specific cyclic N-terminal globin adducts in mice and rats after inhalation exposure to 1,3-butadiene.
1,3-Butadiene is an important industrial chemical used in the production of synthetic rubber and is also found in gasoline and combustion products. It is a multispecies, multisite carcinogen in rodents, with mice being the most sensitive species. 1,3-Butadiene is metabolized to several epoxides that form DNA and protein adducts. Previous analysis of 1,2,3-trihydroxybutyl-valine globin adducts suggested that most adducts resulted from 3-butene-1,2-diol metabolism to 3,4-epoxy-1,2-butanediol, rather than from 1,2;3,4-diepoxybutane. To specifically examine metabolism of 1,3-butadiene to 1,2;3,4-diepoxybutane, the formation of the 1,2;3,4-diepoxybutane-specific adduct N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was evaluated in mice treated with 3, 62.5, or 1250 ppm 1,3-butadiene for 10 days and rats exposed to 3 or 62.5 ppm 1,3-butadiene for 10 days, or to 1000 ppm 1,3-butadiene for 90 days, using a newly developed immunoaffinity liquid chromatography tandem mass spectrometry assay. In addition, 2-hydroxy-3-butenyl-valine and 1,2,3-trihydroxybutyl-valine adducts were determined. The analyses of several adducts derived from 1,3-butadiene metabolites provided new insight into species and exposure differences in 1,3-butadiene metabolism. Mice formed much higher amounts of N,N-(2,3-dihydroxy-1,4-butadiyl)-valine than rats. The formation of 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine was similar in mice exposed to 3 or 62.5 ppm 1,3-butadiene, whereas 2-hydroxy-3-butenyl-valine was 3-fold higher at 1250 ppm. In both species, 1,2,3-trihydroxybutyl-valine adducts were much higher than 2-hydroxy-3-butenyl-valine and N,N-(2,3-dihydroxy-1,4-butadiyl)-valine. Together, these data show that 1,3-butadiene is primarily metabolized via the 3-butene-1,2-diol pathway, but that mice are much more efficient at forming 1,2;3,4-diepoxybutane than rats, particularly at low exposures. This assay should also be readily adaptable to molecular epidemiology studies on 1,3-butadiene-exposed workers.


Initiating regular exercise protects against muscle atrophy from glucocorticoids.
This study was undertaken to examine whether exercise can prevent glucocorticoid-induced muscle atrophy in previously untrained individuals and to evaluate whether the time of hormone administration is a determinant in the muscle's response to glucocorticoids. Female rats were divided into five groups: 1) a sedentary group that received cortisol acetate (CA, 100 mg/kg body wt); 2) a sedentary group that received the dosing vehicle (1% aqueous carboxymethyl cellulose); 3) an exercise group that received CA immediately after each exercise session; 4) an exercise group that received CA 90 min after each exercise session; and 5) an exercise group that received the vehicle. Steroid treatment and exercise (28.7 m/min for 90 min/day) were performed for 11 consecutive days. Initiation of training prevented muscle mass loss by 60% in plantaris (P) muscles and by 25% in gastrocnemius (G) muscles. Time of steroid injection was not related to the muscle sparing response. In the glucocorticoid-treated exercised rats, the activities of citrate synthase, a training marker, increased 60% in P and 37% in G. Thus the exercise appeared to cause a greater recruitment of P muscles. These data support the hypothesis that entering into an exercise program can be effective in retarding glucocorticoid-induced muscle atrophy. The degree of atrophy prevention, however, may be related to the extent that specific muscles are recruited during exercise.


Transvaginal natural orifice transluminal endoscopic surgery in the morbidly obese.
The objective of this study is to assess the safety and efficacy of transvaginal (TV) natural orifice transluminal endoscopic surgery (NOTES) operations in morbidly obese patients. One hundred seven NOTES operations have been performed at our institution to date, of which 17 were completed in patients with body mass index (BMI) between 35 and 45 kg/m(2). These included 14 cholecystectomies, one appendectomy, and two ventral hernia repairs. The patients had average age of 36.2 years (range 19-62 years) and average BMI of 38.9 kg/m(2) (range 35.2-44.9 kg/m(2)). The mean number of previous abdominal operations was 1. The TV cholecystectomies were hybrid NOTES procedures, while TV appendectomy and ventral hernia repair were pure NOTES. All operations were completed with standard straight laparoscopic instruments. The mean operative time was 60 min for cholecystectomy, 41 min for TV appendectomy, and 90 min for ventral hernia repair. No significant difference was encountered between the operative time for NOTES cholecystectomies in obese versus nonobese (60 vs. 61 min, p = 0.86). No conversions to traditional laparoscopy or open surgery were made, and no major complications were encountered. NOTES is an attractive alternative to laparoscopy in female patients with morbid obesity. The procedures are safe and have short operative times, good postoperative outcomes, and improved cosmesis compared with laparoscopy.


Functional analysis of regulatory elements in a plant embryo-specific gene.
Previously we demonstrated the expression of a plant embryo-specific gene encoding the alpha' subunit of beta-conglycinin, a seed storage protein of soybean (Glycine max), in transgenic petunia plants. To examine the regulatory elements that control the expression of this embryo-specific gene (Gmg17.1), a series of deletion mutants was made that contain the alpha'-subunit gene flanked in the 5' direction from +14 nucleotides to -8.5 kilobases (kb) relative to the site of transcription initiation. Each of these deletion mutants was introduced into the genome of petunia cells with the help of Ti-plasmid-derived vectors. Petunia plants were regenerated from transformed cells and expression of the introduced soybean gene was examined. When the alpha'-subunit gene was flanked by 159 nucleotides upstream (Gmg17.1 delta-159), the gene was expressed at a low level in immature embryos. When the gene was flanked by 257 nucleotides upstream of the site of transcription initiation (Gmg17.1 delta-257), a high level of expression was obtained. An additional 8 kb of DNA sequence (which includes the sequence GTGGATAG at -560, which is identical to the core enhancer sequence of simian virus 40 and some animal genes) did not significantly increase the level of expression. The increase in expression level between the delta-159 and delta-257 mutants was at least 20-fold. Analysis of the nucleotides between delta-159 and delta-257 reveals four repeats of a 6-base-pair (G + C)-rich sequence (see formula in text). The deletion Gmg17.1 delta-159 contains a single AACCCA sequence. We suggest that the (G + C)-rich repeats play a critical role in determining the level of expression of the transgenic plants.


An endocytosis defect as a possible cause of proteinuria in polycystic kidney disease.
Because proteinuria has been demonstrated in patients with autosomal-dominant polycystic kidney disease (ADPKD), we have investigated whether proteinuria also occurs in the (cy/+) rat, a widely used model for ADPKD. Increased urinary excretion of proteins, in particular of albumin, can be found in 16-wk-old (cy/+) rats, with a gel electrophoresis pattern compatible with a tubular origin of proteinuria. Using FITC-labeled dextran as an in vivo tracer for renal tubular endosomal function, we could show that portions of cyst-lining epithelia from proximal tubules have lost the ability to endocytose, which is necessary for the reabsorption of low-molecular-weight proteins. By immunohistochemistry, the expression of other proteins implicated in endocytosis, such as the chloride channel ClC-5 and the albumin receptor megalin, correlated well with the presence and absence of FITC-dextran in cysts. As an example of growth factor systems possibly being affected by this endocytosis defect, we could detect increased urinary levels of insulin-like growth factor-I protein in (cy/+) animals. These data indicate that proteinuria and albuminuria in the aforementioned rat model for ADPKD are due to a loss of the endocytic machinery in epithelia of proximal tubular cysts. This may also affect the concentration of different growth factors and hormones in cyst fluids and thus modulate cyst development.


Effects of 1,2-dimethylhydrazine treatment and feeding regimen on rat colonic epithelial cell proliferation.
The present study was designed to test the hypothesis that 1,2-dimethylhydrazine dihydrochloride (DMH) induces preneoplasia in rat colonic epithelium and that this DMH-altered epithelium will respond differently to various nutritional challenges in comparison to normal colonic epithelium. Preneoplasia was arbitrarily defined as an altered and irreversible state of colonic epithelial cell proliferation induced by a carcinogen (DMH). In summary, DMH was found to be specific for the enhancement of rat colonic epithelial cell proliferation compared to other rapidly renewing cell populations, i.e., ileal epithelium and ear epidermis. DMH-induced changes in rat colonic epithelial cell proliferation and crypt cellularity were found to be irreversible following a 2- to 8-week recovery period. The p.o. administration of the solid and liquid diets, regardless of chemical constituents, supported a DMH-induced increase in colonic epithelial cell proliferation; however, a DMH-induced increase in epithelial cell proliferation was not observed in rats maintained on total parenteral nutrition. Thus, the route of administration has a significant influence on epithelial cell proliferation in colonic epithelium of DMH-treated rats. The importance of these results, along with previous studies, is the establishment and initial characterization of an exploitable preneoplastic system in rat colonic epithelium. Particularly revealing was the finding that significant changes in crypt kinetic parameters induced by DMH treatment did not revert to control values following a 2- to 8-week recovery period. Based on an altered and irreversible state of colonic epithelial cell proliferation induced by DMH, it is concluded that: (a) the preneoplastic state is a committed state and is not dependent upon the continued presence of the carcinogen; and (b) all cryptal epithelium is preneoplastic, although not all cells progress to the overtly transformed state. In addition, total parenteral nutrition prevented the expression of a DMH-induced preneoplastic state of altered epithelial cell proliferation.


Functional endoscopic sinus surgery: 5 year follow up and results of a prospective, randomised, stratified, double-blind, placebo controlled study of postoperative fluticasone propionate aqueous nasal spray.
One hundred nine patients with chronic rhinosinusitis underwent functional endoscopic sinus surgery. Seventy seven patients had polyposis. The population was studied prospectively for 5 years postoperatively. Seventy two patients attended the 5 year follow-up visit. At 1, 2, 3, 4 and 5 years of follow-up all outcome measures except olfactory detection thresholds (visual analogue scores, endoscopic findings, nasal mucociliary clearance times, total nasal volumes) were significantly improved compared to preoperative baseline values. Olfactory detection thresholds were significantly improved at 1 and 2 years postoperation. Patient symptom scores were improved in a greater percentage of patients than more objective outcome measures. Thirty eight patients required a total of 88 postoperative rescue medication courses with prednisolone and antibiotic. Twelve patients failed the study as they required at least 1 rescue medication course a month for 2 consecutive months. We demonstrated an 89% 5 year "survival" rate with regards to the risk of failure. The patients were also entered into a randomised, stratified, prospective, double-blind, placebo controlled study of fluticasone propionate aqueous nasal spray 200 mcg twice daily, commencing 6 weeks after FESS, with a 5 year follow-up. The change in overall visual analogue score was significantly better in the FPANS group at 5 years. The changes in endoscopic oedema and polyp scores and in total nasal volumes were significantly better in the FPANS group at 4 years but not 5 years. Last value carried forward analysis demonstrated that changes in endoscopic polyp score and in total nasal volume was significantly better in the FPANS group at 5 years. Significantly more prednisolone rescue medication courses were prescribed in the placebo group. Of the 12 patients who failed the study, 10 were in the placebo group. This difference nearly achieved significance.


Summary of a Consensus Conference on Heart-Liver Transplantation.
Patients with severe heart disease may have co-existing liver disease from various causes. The incidence of combined heart-liver transplant (CHLT) is increasing as more patients with congenital heart disease survive to adulthood and develop advanced heart failure with associated liver disease from chronic right-sided heart or Fontan failure. However, the criteria for CHLT have not been established. To address this unmet need, a virtual consensus conference was organized on June 10, 2022, endorsed by the American Society of Transplantation. The conference represented a collaborative effort by experts in cardiothoracic and liver transplantation from across the United States to assess interdisciplinary criteria for liver transplantation in the CHLT candidate, surgical considerations of CHLT, current allocation system that generally results in the liver following the heart for CHLT, and the optimal post-CHLT management. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical issues related to multi-organ transplantation were also debated. The findings and consensus statements are presented.


Course of sepsis in rats with thyroid dysfunction.
Numerous studies show the relationship between sepsis and thyroid hormones. Virtually all these studies investigate changes in post-sepsis thyroid hormones and the relationship between these changes and the progression of the disease. Our aim in this study was to investigate the progression of sepsis in rats with thyroid dysfunction. The study involved four groups, each containing seven female Wistar albino rats: Group 1: Sham, Group 2: Control (Sepsis), Group 3: Hyperthyroidism-Sepsis, and Group 4: Hypothyroidism-Sepsis. Group 1 only received laparotomy. Group 2 only had sepsis. Sepsis was induced in Group 3 and Group 4 following formation of hyperthyroidism and hypothyroidism, respectively. After 24 hours, relaparotomy and thoracotomy were performed, and tissue and blood samples were drawn. Dysfunctions seen in the liver, lungs, and kidneys during sepsis and other findings of sepsis were milder in the hyperthyroidism group in comparison to both the control and hypothyroidism groups. The results of Simon's grade, histopathological organ damage, and laboratory parameters revealed that the progression of sepsis was milder in the hyperthyroid group than in the hypothyroid and euthyroid groups. The progression in the hypothyroid group was the most severe. Therefore, the results of the study raise the question of whether immediate treatment in cases of hypothyroidism and slow return of thyroid function to normal levels in cases of hyperthyroidism are adequate treatment approaches in patients who may develop sepsis or septic shock." To determine the answer to this question, more detailed studies are required with a higher number of subjects.


[Patterns of maternal-child nursing home-visit].
Here is presented patterns for the maternal-child nursing home-visit, nursing auxiliary personnel. The objective of tris article is to orient nursing auxiliary personeal responsible for maternal-newborn child home visiting. It contains detailed information on what to do when normal as well as abnormal conditions are found.


Asynchrony in host and parasite phenology may decrease disease risk in livestock under climate warming: Nematodirus battus in lambs as a case study.
Mismatch in the phenology of trophically linked species as a result of climate warming has been shown to have far-reaching effects on animal communities, but implications for disease have so far received limited attention. This paper presents evidence suggestive of phenological asynchrony in a host-parasite system arising from climate change, with impacts on transmission. Diagnostic laboratory data on outbreaks of infection with the pathogenic nematode Nematodirus battus in sheep flocks in the UK were used to validate region-specific models of the effect of spring temperature on parasite transmission. The hatching of parasite eggs to produce infective larvae is driven by temperature, while the availability of susceptible hosts depends on lambing date, which is relatively insensitive to inter-annual variation in spring temperature. In southern areas and in warmer years, earlier emergence of infective larvae in spring was predicted, with decline through mortality before peak availability of susceptible lambs. Data confirmed model predictions, with fewer outbreaks recorded in those years and regions. Overlap between larval peaks and lamb availability was not reduced in northern areas, which experienced no decreases in the number of reported outbreaks. Results suggest that phenological asynchrony arising from climate warming may affect parasite transmission, with non-linear but predictable impacts on disease burden. Improved understanding of complex responses of host-parasite systems to climate change can contribute to effective adaptation of parasite control strategies.


The Dual Nature of Social Media: Examining the Direction of Causal Flow Between Fear of Missing Out and Social Media Use.
The dual (bidirectional) nature of social media suggests that fear-of-missing-out (FOMO) leads to greater social media use (SMU). In turn, higher levels of SMU lead to heightened FOMO. Ironically, individuals use social media to assuage their FOMO but end up with higher levels of FOMO after being exposed to a wide variety of social opportunities, where they may not have been included. The present research examines the hypothesized bidirectional causal flow between FOMO and SMU. Extant research involving FOMO has been largely correlational. In Study 1, FOMO was manipulated and found to increase reported levels of SMU. Study 2 manipulated SMU, which led to higher levels of FOMO. It appears that, regarding FOMO, social media does exhibit a dual (bidirectional) nature.


Application of spectral phase shaping to high resolution CARS spectroscopy.
By spectral phase shaping of both the pump and probe pulses in coherent anti-Stokes Raman scattering (CARS) spectroscopy we demonstrate the extraction of the frequencies, bandwidths and relative cross sections of vibrational lines. We employ a tunable broadband Ti:Sapphire laser synchronized to a ps-Nd:YVO mode locked laser. A high resolution spectral phase shaper allows for spectroscopy with a precision better than 1 cm(-1) in the high frequency region around 3000 cm(-1). We also demonstrate how new spectral phase shaping strategies can amplify the resonant features of isolated vibrations to such an extent that spectroscopy and microscopy can be done at high resolution, on the integrated spectral response without the need for a spectrograph.


Effects of garcinia cambogia (Hydroxycitric Acid) on visceral fat accumulation: a double-blind, randomized, placebo-controlled trial.
(-)-Hydroxycitric acid (HCA) is an active ingredient extracted from the rind of the Indian fruit Garcinia cambogia. It inhibits adenosine triphosphate citrate lyase and has been used in the treatment of obesity. The primary end point of this study was the effects of 12 weeks of G cambogia extract administration on visceral fat accumulation. The secondary end points were body indices (including height, body weight, body mass index [BMI], waist and hip circumference, and waist-hip ratio) and laboratory values (including total cholesterol, triacylglycerol, and free fatty acid). This study was performed according to a double-blind, randomized, placebo-controlled, parallel-group design. Subjects aged 20 to 65 years with a visceral fat area >90 cm(2) were enrolled. Subjects were randomly assigned to receive treatment for 12 weeks with G cambogia (containing 1000 mg of HCA per day) or placebo. At the end of the treatment period, both groups were administered placebo for 4 weeks to assess any rebound effect. Each subject underwent a computed tomography scan at the umbilical level at -2, 0, 12, and 16 weeks. Forty-four subjects were randomized at baseline, and 39 completed the study (G cambogia group, n = 18; placebo group, n = 21). At 16 weeks, the G cambogia group had significantly reduced visceral, subcutaneous, and total fat areas compared with the placebo group (all indices P<0.001). No severe adverse effect was observed at any time in the test period. There were no significant differences in BMI or body weight at week 12, but there were slight numeric decreases in body weight and BMI in men. There were no signs of a rebound effect from week 12 to week 16. G cambogia reduced abdominal fat accumulation in subjects, regardless of sex, who had the visceral fat accumulation type of obesity. No rebound effect was observed. It is therefore expected that G cambogia may be useful for the prevention and reduction of accumulation of visceral fat.


Biomass allocation and nutrients balance related to the concentration of Nitrogen and Phosphorus in Salvinia auriculata (Salviniaceae).
Aquatic plants can use differential allocation (trade-off) of carbon among their structures depending on the nutrition concentration. Given that N and P are limiting in the growth of plants, our questions were: Are the N and P concentrations in S. auriculata related to the biomass allocation to its structures? Is a differential allocation of N and P between floating and submerged leaves? We evaluated the relation between the nutrients and the biomass allocation, and the trade-off among the leaves using the Spearman correlation. Our results showed that N and P concentrations in S. auriculata are related to the biomass allocation to its structures, and that there is no trade-off of these nutrients between "shoot and root". Thus, we can see the importance of N and P concentration in the biomass of S. auriculata, and why this plant is capable to development in different environments as a weedy.


Improving rigor and reproducibility in nonhuman primate research.
Nonhuman primates (NHPs) are a critical component of translational/preclinical biomedical research due to the strong similarities between NHP and human physiology and disease pathology. In some cases, NHPs represent the most appropriate, or even the only, animal model for complex metabolic, neurological, and infectious diseases. The increased demand for and limited availability of these valuable research subjects requires that rigor and reproducibility be a prime consideration to ensure the maximal utility of this scarce resource. Here, we discuss a number of approaches that collectively can contribute to enhanced rigor and reproducibility in NHP research.


A cell line resource derived from honey bee (Apis mellifera) embryonic tissues.
A major hindrance to the study of honey bee pathogens or the effects of pesticides and nutritional deficiencies is the lack of controlled in vitro culture systems comprised of honey bee cells. Such systems are important to determine the impact of these stress factors on the developmental and cell biology of honey bees. We have developed a method incorporating established insect cell culture techniques that supports sustained growth of honey bee cells in vitro. We used honey bee eggs mid to late in their embryogenesis to establish primary cultures, as these eggs contain cells that are progressively dividing. Primary cultures were initiated in modified Leibovitz's L15 medium and incubated at 32(°)C. Serial transfer of material from several primary cultures was maintained and has led to the isolation of young cell lines. A cell line (AmE-711) has been established that is composed mainly of fibroblast-type cells that form an adherent monolayer. Most cells in the line are diploid (2n = 32) and have the Apis mellifera karyotype as revealed by Giemsa stain. The partial sequence for the mitochondrial-encoded cytochrome c oxidase subunit I (Cox 1) gene in the cell line is identical to those from honey bee tissues and a consensus sequence for A. mellifera. The population doubling time is approximately 4 days. Importantly, the cell line is continuously subcultured every 10-14 days when split at a 1:3 ratio and is cryopreserved in liquid nitrogen. The cell culture system we have developed has potential application for studies aimed at honey bee development, genetics, pathogenesis, transgenesis, and toxicology.


Sodium valproate: monotherapy and polytherapy.
Of the 605 patients seen since 1973, 336 patients have been treated with sodium valproate (VPA) alone or in combination with drugs other than carbamazepine (CBZ). Of these 336, 240 have been on monotherapy, of whom 200 are seizure-free. Follow up has been longer than 3 years in 78%. Complete control of seizures has been achieved in more than 80% of patients with absence, myoclonic, and primary tonic-clonic seizures, in 72% of those with photosensitive epilepsy including eyelid myoclonia, and in 47% of partial epilepsies, for which carbamazepine was the initial drug of choice. Only 21% of those with myoclonic astatic epilepsy have become free from seizures. At first VPA was given twice daily, but in recent years it was given once daily, as this was more effective. Reasons for failure of VPA therapy are given. Side effects in 436 patients (100 more patients were added for this assessment only) were uncommon, though where they did occur, weight increase was the most frequent. Platelets were reduced without clinical problems. There were no severe hepatic disorders. Serum levels were assessed in seizure-free patients, and the optimum level was between 60 and 120 mg/L (most patients received between 20 and 30 mg/kg). VPA was given during 30 pregnancies, and there was no evidence of teratogenicity on monotherapy. VPA is most effective in primary generalized epilepsy, especially if given as the sole antiepileptic drug. If the daily dose does not exceed 40 mg/kg or 2.5 g, it is singularly free from serious side effects.


Functional neuroimaging of normal human sleep by positron emission tomography.
Functional neuroimaging using positron emission tomography has recently yielded original data on the functional neuroanatomy of human sleep. This paper attempts to describe the possibilities and limitations of the technique and clarify its usefulness in sleep research. A short overview of the methods of acquisition and statistical analysis (statistical parametric mapping, SPM) is presented before the results of PET sleep studies are reviewed. The discussion attempts to integrate the functional neuroimaging data into the body of knowledge already acquired on sleep in animals and humans using various other techniques (intracellular recordings, in situ neurophysiology, lesional and pharmacological trials, scalp EEG recordings, behavioural or psychological description). The published PET data describe a very reproducible functional neuroanatomy in sleep. The core characteristics of this 'canonical' sleep may be summarized as follows. In slow-wave sleep, most deactivated areas are located in the dorsal pons and mesencephalon, cerebellum, thalami, basal ganglia, basal forebrain/hypothalamus, prefrontal cortex, anterior cingulate cortex, precuneus and in the mesial aspect of the temporal lobe. During rapid-eye movement sleep, significant activations were found in the pontine tegmentum, thalamic nuclei, limbic areas (amygdaloid complexes, hippocampal formation, anterior cingulate cortex) and in the posterior cortices (temporo-occipital areas). In contrast, the dorso-lateral prefrontal cortex, parietal cortex, as well as the posterior cingulate cortex and precuneus, were the least active brain regions. These preliminary studies open up a whole field in sleep research. More detailed explorations of sleep in humans are now accessible to experimental challenges using PET and other neuroimaging techniques. These new methods will contribute to a better understanding of sleep functions.


[Nongynecological surgical procedures performed by an oncological gynecology service].
From March, 1987 to July 1990, 1,568 surgical procedures, were done at Oncological Gynecology Service; 206 of them (13.1%) were considered as "non-gynecological" surgical procedures; 182 (88.3%) were secondary to a malignity diagnosis, being the most frequent one ovarian carcinoma (54.4%). As to benign lesions, 11.7% caused "non gynecological" surgery, most frequent were severe pelvic adhesions, 41.6%, and severe endometriosis, 25%. "Non-gynecological" surgical procedure carried out most frequently was pelvic lymphadenectomy. Morbidity was 3.8%, and mortality, 0.48% due to acute myocardial infarction. The acceptance for oncologic gynecologist is justified in this series, based on survival and morbi-mortality, which permits the participation in a multidisciplinary team.


Association of adenovirus infection with human obesity.
We previously reported that chickens infected with the avian adenovirus SMAM-1 developed a unique syndrome characterized by excessive intra-abdominal fat deposition accompanied by paradoxically low serum cholesterol and triglyceride levels. There have been no previous reports of avian adenoviruses infecting humans. We screened the serum of 52 humans with obesity in Bombay, India, for antibodies against SMAM-1 virus using the agar gel precipitation test (AGPT) method. Bodyweights and serum cholesterol and triglyceride levels were compared in SMAM-1-positive (P-AGPT) and SMAM-1-negative (N-AGPT) groups. Ten subjects were positive for antibodies to SMAM-1, and 42 subjects did not have antibodies. The P-AGPT group had a significantly higher bodyweight (p < 0.02) and body mass index (p < 0.001) (95.1 +/- 2.1 kg and 35.3 +/- 1.5 kg/m2, respectively) compared with the N-AGPT group (80.1 +/- 0.6 kg and 30.7 +/- 0.6 kg/m2, respectively). Also, the P-AGPT group had significantly lower serum cholesterol (p < 0.02) and triglyceride (p < 0.001) values (4.65 mmol/L and 1.45 mmol/L, respectively) compared with the N-AGPT group (5.51 mmol/L and 2.44 mmol/L, respectively). Two subjects positive for SMAM-1 antibodies had antibodies against each others' serum, suggesting the presence of antigens in one or both. When these two serum samples were inoculated into chicken embryos, macroscopic lesions compatible with SMAM-1 infection developed. The inoculation of serum from N-AGPT subjects did not produce such lesions. The presence of increased obesity, antibodies to SMAM-1, reduced levels of blood lipids, and viremia that produces a typical infection in chicken embryos suggests that SMAM-1, or a serologically similar human virus, may be involved in the cause of obesity in some humans.


The Impact of Obesity on Mortality and Other Outcomes in Patients With Nonvariceal Upper Gastrointestinal Hemorrhage in the United States.
To quantify in patients with nonvariceal upper gastrointestinal hemorrhage (NVUGIH) the relationship between obesity and mortality, disease severity, treatment modalities, and resource utilization. NVUGIH is the most common gastrointestinal emergency. Adults with a principal diagnosis of NVUGIH were selected from the 2014 National Inpatient Sample. The primary outcome was in-hospital mortality. Secondary outcomes were hemorrhagic shock, prolonged mechanical ventilation (PMV), upper endoscopy [esophagogastroduodenoscopy (EGD)], radiologic treatment, surgery, length of hospital stay (LOS), and total hospitalization costs and charges. Confounders were adjusted for using multivariable regression analyses. In total, 227,480 admissions with NVUGIH were included, 11.70% of whom were obese. Obese and nonobese patients had similar odds of mortality (aOR: 0.88; 95% confidence interval [CI]: 0.69-1.12; P=0.30), EGD within 24 hours of admission (aOR: 0.95; CI: 0.89-1.01; P=0.10), radiologic treatment (aOR: 1.06; CI: 0.82-1.35; P=0.66), and surgery (aOR: 1.27; CI: 0.94-1.70; P=0.11). However, obese patients had higher odds of shock (aOR: 1.30; CI: 1.14-1.49; P<0.01), PMV (aOR: 1.39; CI: 1.18-1.62; P<0.01), undergoing an EGD (aOR: 1.27; CI: 1.16-1.40; P<0.01), needing endoscopic therapy (aOR: 1.18; CI: 1.09-1.27; P<0.01), a longer LOS (0.31 d; CI: 0.16-0.46 d; P<0.01), higher costs ($1075; CI: $636-$1514; P<0.01), and higher charges ($4084; CI: $2060-$6110; P<0.01) compared with nonobese patients. Obesity is not an independent predictor of NVUGIH mortality. However, obesity is associated with a more severe disease course (shock and PMV), higher rates of EGD and endoscopic therapy use, and significant increases in resource utilization (hospital LOS, total hospitalization costs, and charges).


Update on Pediatric Medial Epicondyle Fractures.
The ideal evaluation and treatment of pediatric patients with medial epicondyle fractures remain controversial. It is important to examine the most recent literature and provide an update on the current clinical practices, imaging modalities, treatment techniques, outcomes, and complications associated with displaced pediatric medial epicondyle fractures. There remains substantial variability across recommended treatment options and the outcomes between surgical versus nonsurgical management of these injuries. Despite the lack of consensus regarding management of pediatric medial epicondyle fractures, both nonsurgical and surgical approaches have demonstrated equivocal results.


[Modern non-drug approaches to human sleep regulation].
Existing approaches to non-drug regulation and induction of human sleep are analyzed with an attempt of their classification. The main attention is paid to the methods that utilize modern computer technologies of registration and analysis of various characteristics of human organism functioning, basically to the electroencephalogram (EEG). Normal human sleep EEG correlates and their changes during different sleep stages are reviewed. Modern opportunities to regulate and induce human sleep via utilization of different EEG characteristics are analyzed.


The Feasibility and Acceptability of an Online CPD Programme to Enhance PE Teachers' Knowledge of Muscular Fitness Activity.
Schools provide an opportunity to enhance muscular fitness of English youth during physical education (PE). Continued professional development (CPD) among teachers may improve muscular fitness activity delivery in schools. This study sought to assess the feasibility and acceptability of an online CPD programme to enhance PE teachers' knowledge of muscular fitness activity. Co-production of an online CPD platform was undertaken with five secondary school PE teachers. A quasi-experimental pre-post control group design for the CPD was adopted (CPD group n = 76, control n = 32). Upon CPD completion feedback was solicited for qualitative analysis. Pre-and-post CPD knowledge quiz data were available from 65 participants (55.4% male). The median knowledge quiz change score was significantly higher in the CPD group than in the wait list control group (CPD score vs. control score; U =37, z = -5.96, p < 0.01). Three primary themes reflecting factors associated with the acceptability and feasibility were (1) practical application, (2) support and resources, and (3) knowledge and confidence. Co-production of an online CPD programme can improve knowledge and affect practice. PE teachers that completed the CPD reported the online platform was beneficial to overcoming the limitations of face-to-face CPD such as time and financial constraints and suggested the content covered was beneficial and appropriate to their teaching. Future work is required to establish links between teachers' learning following CPD, the translation into PE practice and student MF outcomes.


Repair of abdominal aortic aneurysms: preoperative imaging and evaluation.
Imaging is a critical component of the pre-procedure evaluation and planning of endovascular aneurysm repair (EVAR). Imaging is the mainstay for proper assessment of procedural candidacy, relevant vascular anatomy, device selection, and surgical approach. Computed tomography angiography (CTA) has long been considered the preferred modality for pre-operative imaging and evaluation prior to EVAR. Recently, advances in image quality and software technology have further enhanced the proceduralist's ability to plan and perform EVAR. In this review, we highlight the current state of the art to provide interventionalists a contemporary assessment of the available tools for pre-operative imaging and evaluation prior to EVAR.


Early Clinical and Functional Outcome of Rotator Cuff Tendinopathy of the Shoulder Treated with Platelet Rich Plasma Injection.
Rotator cuff tendinitis has been treated using various methods including physiotherapy, steroid injections and recently platelet rich plasma (PRP). Most of these methods aim at giving symptomatic relief rather than addressing the pathology. There is no clear consensus over the benefit of using PRP for tendinitis. We decided to do a prospective clinical study to demonstrate the efficacy of PRP and study the functional outcome in the treatment of rotator cuff tendinopathy. Patients with shoulder pain for more than three months not responding to NSAIDs or physiotherapy with a diagnosis of rotator cuff tendinitis, confirmed by MRI, were included in the study. Patients with rotator cuff tear or any other shoulder pathology were excluded. We included a total of 30 patients who received 5ml of landmark guided PRP injection in the subacromial space followed by a six-week exercise program. Patients were followed-up at 3, 6 and 12 weeks. and were assessed clinically using the VAS, SPADI and Constant and Murley Score. VAS score of patients improved from a pre injection score of 7.4 to a score of 1.9 in the 12th week. The mean SPADI score and Constant score improved from a pre injection score of 73.33 and 39.57 to a post injection score of 18.1 and 86.47, respectively. Platelet Rich Plasma injections showed good to excellent early results, in patients with rotator cuff tendinopathy with improvement in VAS, SPADI and Constant scores.


Diverse biological effects of electromagnetic-treated water.
The effects of water treated with an electromagnetic field (EMF) were investigated on two biological systems, humans and plants. Purified de-ionised water was treated by (1) boiling, (2) exposure to microwave radiation, and (3) low frequency electromagnetic oscillation molecular resonance effect technology (MRET), before being used to prepare media for culturing human peripheral blood mononuclear cells (PBMC) from three healthy females. Our results indicated that PBMC culture in MRET-activated medium showed significantly less oxidative metabolism when compared to media prepared from other types of water. As for the effects on soybean, our results indicated that both MRET- and microwave-treated water greatly enhanced the length of the root. These results suggested that electromagnetic-treated water can have diverse biological effects on both animal and plant cells. Since these effects are related to the 'Memory of Water', hypothesis which has been suggested as an explanation of the action of high homeopathic dilutions, our finding warrant a further investigation on the mechanisms of various types of physically conditioned water on specific cellular activities.


Patients' Self-Reported Disability Weights of Top-Ranking Diseases in Thailand: Do They Differ by Socio-Demographic and Illness Characteristics?
Little is known about the impact of methodological decisions on estimating disability weights among patients with mental and physical disorders, and the effects of socio-demographic status on the estimation of these weights. A cross-sectional study was conducted in three hospitals in southern Thailand to describe the disability weights based on different valuation methods. Altogether, 150 patients with major depressive disorder, 150 with alcohol use disorder, and 150 with osteoarthritis with varying levels of severity were recruited. Using a face-to-face interview, all patients completed a visual analogue scale (VAS) and were randomly assigned to complete either the European Quality of Life-5 Dimensions (EQ-5D) or Time-trade-off (TTO) instrument to estimate their current utility score, which was consequently transformed to a disability weight. Significant differences were found between disability weights derived from the three instruments for the same disease, with the VAS providing the highest and EQ-5D the lowest weights. Patients with major depressive disorder had the highest disability weight while those with osteoarthritis had lowest by most methods. Patients' socio-demographics do not affect how they perceive their disability or health condition. Our findings highlight the importance of carefully selecting methods of valuing disability weights, which can rely on disease specific conditions.


Advanced paternal age is associated with alterations in discrete behavioural domains and cortical neuroanatomy of C57BL/6J mice.
Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia. A previous study in mice suggested that the offspring of aged sires have altered locomotion and avoidance learning. The aim of the current study was to conduct a comprehensive behavioural screen in adult offspring of mice of APA. We also examined brain morphology in neonate and adult mice. The adult offspring of 12- to 18-month-old (APA) and 4-month-old (control) male C57BL/6J mice underwent a behavioural test battery comprising tests for locomotion, anxiety, exploration, social behaviour, learned helplessness and sensorimotor gating. The brains of these mice were collected at 3 months and imaged ex vivo using a 16.4 T MRI scanner to assess gross neuroanatomy. Neuroanatomy was also examined at birth in a separate cohort of animals. Overall, the APA mouse model was associated with subtle behavioural changes and altered cortical morphology. The behavioural phenotype of female APA mice included increased anxiety-related behaviour, increased exploration and decreased learned helplessness compared to control females. Male APA mice had thinner cortices at birth and increased cortical volume as adults. This animal model may assist in exploring the mechanism of action linking APA with disorders such as schizophrenia and autism.


Diffusive and directional intracellular dynamics measured by field-based dynamic light scattering.
Quantitative measurement of diffusive and directional processes of intracellular structures is not only critical in understanding cell mechanics and functions, but also has many applications, such as investigation of cellular responses to therapeutic agents. We introduce a label-free optical technique that allows non-perturbative characterization of localized intracellular dynamics. The method combines a field-based dynamic light scattering analysis with a confocal interferometric microscope to provide a statistical measure of the diffusive and directional motion of scattering structures inside a microscopic probe volume. To demonstrate the potential of this technique, we examined the localized intracellular dynamics in human epithelial ovarian cancer cells. We observed the distinctive temporal regimes of intracellular dynamics, which transitions from random to directional processes on a timescale of ~0.01 sec. In addition, we observed disrupted directional processes on the timescale of 1 approximately 5 sec by the application of a microtubule polymerization inhibitor, Colchicine, and ATP depletion.


The terminal RNA stem-loop structure and 80 bp of spacer DNA are required for the formation of 3' termini of sea urchin H2A mRNA.
We have studied the exact sequence requirement for the formation of 3' termini of the sea urchin H2A mRNA in frog oocyte injection experiments. Point mutations destroying the symmetry of the inverted DNA repeat in the mRNA trailer coding sequences prevent the generation of genuine 3' termini. Mutants containing complementary base changes are pseudorevertants and allow the production of H2A mRNA with faithful 3' termini at wild-type levels. Our transcription analyses show that it is primarily the sequence of the transcribed strand that decides whether or not true 3' mRNA termini are produced. This is evidence that an RNA stem-loop structure, rather than a DNA cruciform, is essential for this process. Spacer sequences are absolutely required, because in their absence only H2A mRNA with spacer transcript extensions are found. Once the canonical CAAGAAAGA and flanking sequences are linked to the H2A gene, H2A messenger is synthesized at a suboptimal rate, which can be increased to wild-type levels by the addition of 80 bp of the spacer immediately adjacent to the H2A gene.


[External version of breech presentation--a possibility for lowering the rate of cesarean section and infant morbidity].
Between 1979 and 1985 a total of 8641 children were born at the gynecological clinic in Winterthur, 388 of them (4.5%) from breech presentation. All of these were evaluated with regard to external version, and conditions for an attempt at version were satisfied in 97 cases. The principal prerequisite was a gestational age of at least 37 weeks. External version was accomplished in 39 of the 97 cases (40.2%). Complications encountered were drops in fetal heart tone or bradycardias in 26 cases (26.8%); the attempt at version was abandoned for this reason in 22 cases. In one case premature detachment of the normally implanted placenta occurred 6 days after successful external version, and in one case an emergency cesarean section had to be performed owing to persistent bradycardia. In a further case intrauterine fetal death was established 18 hours after successful version on the basis of an absence of fetal movement, though no cause of death could be found. Among the 39 cases in which version was successful a cesarean section was only necessary in one (2.5%), as opposed to 21 in the 58 cases (36.2%) in which the attempt at version failed. Neonatal fetal condition (Apgar score and umbilical blood gas analysis) revealed that neonates born from vertex presentation are subject to very considerably less stress. The international literature is discussed and compared. It is found that there has been a change of trend from a tendency to reject external version in the 1970s to a majority favoring it in the 1980s.(ABSTRACT TRUNCATED AT 250 WORDS)


Morphological and Molecular Diagnosis of Necator americanus and Ancylostoma ceylanicum Recovered from Villagers in Northern Cambodia.
Human hookworm infections caused by adult Ancylostoma spp. and Necator americanus are one of the most important tropical diseases. We performed a survey of intestinal helminths using the Kato-Katz fecal examination technique targeting 1,156 villagers residing in 2 northern provinces (Preah Vihear and Stung Treng) of Cambodia in 2018. The results revealed a high overall egg positive rate of intestinal helminths (61.9%), and the egg positive rate of hookworms was 11.6%. Nine of the hookworm egg positive cases in Preah Vihear Province were treated with 5-10 mg/kg pyrantel pamoate followed by purging with magnesium salts, and a total of 65 adult hookworms were expelled in diarrheic stools. The adult hookworms were analyzed morphologically and molecularly to confirm the species. The morphologies of the buccal cavity and dorsal rays on the costa were observed with a light microscope, and the nucleotide sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene were analyzed. The majority of the hookworm adults (90.7%) were N. americanus, whereas the remaining 9.3% were Ancylostoma ceylanicum, a rare hookworm species infecting humans. The results revealed a high prevalence of hookworm infections among people in a northern part of Cambodia, suggesting the necessity of a sustained survey combined with control measures against hookworm infections.


Modulation of the orodigestive tract microbiome in HIV-infected patients.
More than 37 million people are living with human immunodeficiency virus 1 (HIV), and more people than ever received lifesaving antiretroviral therapy worldwide. HIV-1 infection disrupts the intestinal immune system, leading to microbial translocation and systemic immune activation. We investigated the impact of HIV-1 infection on the GI microbiome and its association with host immune activation. The data indicated that the microbiome was different in HIV-positive and HIV-negative individuals. The initial sequence analysis of saliva indicated that there were major differences in the phyla of Bacteroidetes, Firmicutes, Proteobacteria, and TM7. Phylum Tenericutes was only seen in HIV-positive saliva. At the family level, we identified differences in Streptococcacea, Prevotellaceae, Porphyromonadaceae, and Neisseriaceae, whereas data from various sites in GI tract indicated that Prevotella melaninigencia, Fusobacterium necrophorum, Burkholderia, Bradyrhizobium, Ralstonia, and Eubacterium biforme were predominant but differentially present at various sites. Furthermore, there was a decrease in seven proteins associated with the alternative complement pathway and an increase in 6 proteins associated with the lectin and classical complement pathways. The correlation with a shift in complement pathways suggests that compromised immunity could be responsible for the observed dysbiosis in the GI microbiome.


Are prorocentroid dinoflagellates monophyletic? A study of 25 species based on nuclear and mitochondrial genes.
The dinoflagellate sub-class Prorocentrophycidae has a distinct morphology, lacking the typical dinoflagellate cell structure of a clear cingulum and sulcus. It includes species that produce the toxin okadaic acid. Despite its uniqueness, the group has been found polyphyletic in some previous molecular phylogenetic studies. We have re-investigated the phylogeny of this sub-class by culturing and sequencing new strains, comparing sequences from three genes, the mitochondrial cytochrome c oxidase subunit 1 (cox 1) and the nuclear large and small subunit rRNA (LSU and SSU) encoding genes. We analyzed sequences from twenty-five named and two still undescribed species of Prorocentrophycidae. We used newly recognized features of the secondary structure to align regions of the LSU rRNA. The phylogeny based on cox 1 provided the most well-supported tree and showed strong support for the monophyly of prorocentroid dinoflagellates, while the LSU phylogeny was inconclusive. As in previous studies, phylogeny based on SSU shows the group to appear paraphyletic, however, support values were low. Two strongly supported sub-clades were consistently identified. Benthic and planktonic modes appear to have evolved on multiple occasions within both clades of Prorocentriphycidae. The capability to synthesize toxins appears to have arisen early in prorocentroid evolution and, in particular, okadaic acid synthesis is present in some, but not all, members of Clade 2. The D2a region of the LSU rRNA appears to have developed a deletion in three definable steps during prorocentroid evolution. While the phylogenies inferred from the three genes were not congruent, our results give reserved support to the monophyly of the group.


[Prophylactics and treatment of postoperative hernias of the lateral abdominal walls using polypropylene endoprosthesis].
An analysis of complex examination and treatment of 151 patients after planned and performed surgical interventions on organs of the retroperitoneal space was made. The patients were divided into 4 groups. The first group (of comparison) included 46 patients who were treated by lumbotomy for different diseases of organs of the urinary system. In 35 patients of the second group (prophylactics) the indications were determined and in 20 patients preventive endoprosthesis of the lateral abdominal wall using polypropylene endoprosthesis was fulfilled. Herniotomy with plasty of the lateral abdominal wall using local tissues was fulfilled in 30 patients. Prosthesing hernioplasty of the lateral abdominal wall was fulfilled in 40 patients of the main group. It was found that preventive endoprosthesis of the lateral abdominal wall allowed prevention of progressing anatomo-functional i/isufficiency and the appearance of postoperative hernias. The application of polypropylene endoprosthesis for the treatment of postoperative hernias allows obtaining 36.4% more good results as compared with the control group, 21.7% decreased number of satisfactory results and no recurrent hernias.


Sustained Low Incidence Rates of Central Line-Associated Blood Stream Infections in the Intensive Care Unit.
Central line-associated bloodstream infection (CLABSI) is an important cause of increased morbidity and mortality in ICUs. The occurrence of CLABSI in significantly higher in developing countries and contributes to the burden of healthcare-associated infections. This prospective study was carried out from January 2016 to December 2019 in the intensive care unit at King Faisal Medical Complex in Taif, Saudi Arabia. The Society for Healthcare Epidemiology of America/Infectious Diseases Society of America (SHEA/IDSA) recommendations were introduced and implemented during 2017-2019. In the post-intervention period, observation of hand hygiene, CLABSI bundle compliance, and benchmarking of CLABSI rates were carried out. The CLABSI incidence rate was 1.12/1,000 central-line days, with a 0.51 utilization ratio in the pre-intervention period. This dropped to 0.46/1,000 central line days with a 0.44 utilization ratio in the post-intervention period. This reduction was also confirmed in benchmarking with National Healthcare Safety Network (NHSN) (50th-75th) percentile pre-intervention vs (25th-50th) percentile post-intervention. Institutional risk assessment revealed a formal educational program as a potential need for improvement. The CLABSIs were caused predominantly by multidrug-resistant Klebsiella pneumoniae. We observed a reduction and sustained low incidence rate of CLABSI benchmarking to NHSN for 3 years after implementation of the basic SHEA/IDSA recommendations.


Elevated granulocyte manganese in rheumatoid arthritis and other connective tissue diseases.
Higher than normal amounts (p less than 0.001) of manganese were found in granulocytes isolated from patients with rheumatoid arthritis, other inflammatory arthritides, and scleroderma, while erythrocytes and platelets contained normal amounts of manganese. The cause of manganese accumulation is not known but evidently is linked to the intensity of the inflammatory process since significant positive correlations (p less than 0.001) were seen between erythrocyte sedimentation rate or serum haptoglobin and granulocyte manganese. During corticosteroid therapy granulocyte manganese started to return to normal levels but the relative changes were modest. Strong positive correlations (p less than 0.001) were found between granulocyte manganese and granulocyte stores of calcium and iron, suggesting a close relationship in the cellular regulation of these elements in chronic inflammatory conditions.


Stromal cell cadherin-11 regulates adipose tissue inflammation and diabetes.
M2 macrophages, innate lymphoid type 2 cells (ILC2s), eosinophils, Tregs, and invariant NK T cells (iNKT cells) all help to control adipose tissue inflammation, while M1 macrophages, TNF, and other inflammatory cytokines drive inflammation and insulin resistance in obesity. Stromal cells regulate leukocyte responses in lymph nodes, but the role of stromal cells in adipose tissue inflammation is unknown. PDGFRα+ stromal cells are major producers of IL-33 in adipose tissue. Here, we show that mesenchymal cadherin-11 modulates stromal fibroblast function. Cadherin-11-deficient mice displayed increased stromal production of IL-33, with concomitant enhancements in ILC2s and M2 macrophages that helped control adipose tissue inflammation. Higher expression levels of IL-33 in cadherin-11-deficient mice mediated ILC2 activation, resulting in higher IL-13 expression levels and M2 macrophage expansion in adipose tissue. Consistent with reduced adipose tissue inflammation, cadherin-11-deficient mice were protected from obesity-induced glucose intolerance and adipose tissue fibrosis. Importantly, anti-cadherin-11 mAb blockade similarly improved inflammation and glycemic control in obese WT mice. These results suggest that stromal fibroblasts expressing cadherin-11 regulate adipose tissue inflammation and thus highlight cadherin-11 as a potential therapeutic target for the management of obesity.


Molecular Identification and Antimicrobial Activity of Vaginal Lactobacillus sp.
The genus Lactobacillus has recently been the focal point of researchers due to their ability to produce secondary metabolites with antimicrobial effects. The aim of this study was to identify vaginal Lactobacillus sp. by analyzing 16S rRNA gene sequence, to investigate into antimicrobial activities of secondary metabolites produced by these isolates and to determine the quantities of lactic acid, acetic acid and hydrogen peroxide in secondary metabolites using High-Performance Liquid Chromatography. Antimicrobial activities of secondary metabolites were investigated against test microorganisms using Agar Well Diffusion and Agar Spot Methods. According to the results, 18 L. crispatus, 17 L. gasseri, 5 L. jensenii, 4 L. vaginalis, 3 L. fermentum, 2 L. coleohominis, 1 L. saerimneri, 1 L. reuteri, 1 L. johnsonii and 1 L. helveticus were identified. Isolates were frequently found to be effective against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae RSKK 578 and Bacillus subtilis ATCC 6633. None of the isolates showed activity against Staphylococcus aureus ATCC 43300, S. epidermidis ATCC 12228, S. epidermidis ATCC 35984 and Candida albicans ATCC 10231. Secondary metabolites of all tested isolates contain hydrogen peroxide between 7.306 and 0.33 µg/µL range. It was found that the secondary metabolites of some isolates contained both acetic and lactic acid, while some of them contained either acetic or lactic acid.


Associations of sport participation with self-perception, exercise self-efficacy and quality of life among children and adolescents with a physical disability or chronic disease-a cross-sectional study.
Little evidence is available about how sports participation influences psychosocial health and quality of life in children and adolescents with a disability or chronic disease. Therefore, the aim of the current study is to assess the association of sports participation with psychosocial health and with quality of life, among children and adolescents with a disability. In a cross-sectional study, 195 children and adolescents with physical disabilities or chronic diseases (11% cardiovascular, 5% pulmonary, 8% metabolic, 8% musculoskeletal/orthopaedic, 52% neuromuscular and 9% immunological diseases and 1% with cancer), aged 10-19 years, completed questionnaires to assess sports participation, health-related quality of life (DCGM-37), self-perceptions and global self-worth (SPPC or SPPA) and exercise self-efficacy. Regression analyses showed that those who reported to participate in sports at least twice a week had more beneficial scores on the various indicators compared to their peers who did not participate in sport or less than twice a week. Those participating in sports scored better on all scales of the DCGM-37 scale, on the scales for feelings of athletic competence and children but not adolescents participating in sports reported greater social acceptance. Finally, we found a strong association between sport participation and exercise self-efficacy. This study provides the first indications that participating in sports is beneficial for psychosocial health among children and adolescents with a disability. However, more insight is needed in the direction of the relationships.


[A free radial forearm flap in oral cavity reconstruction].
A relatively recent method for reconstruction of the oral cavity after tumor removal employs the use of revascularized free flaps. In particular, the Radial Forearm Flap has gained significant international recognition. After a review of the history of this procedure, the authors describe the essential aspects of the technique including what is involved in removal as well as in microanastomosis and reconstruction. In addition, the paper also deals with operative patient monitoring, prevention and treatment of any complications. Finally, a series of 10 cases is presented all of which underwent surgery at the E.N.T. Division of the Varese Hospital. The case study presents the oncological and functional results and emphasizes the technical details of the entire sampling. The purpose of this work has been to demonstrate that this procedure can be used by an E.N.T. surgical staff without requiring input from an outside team of specialists. Although this technique is difficult and somewhat limited, it must be considered one of the most innovative proposals in the field of plastic, reconstructive surgery of the head and neck.


Conservation and canalization of gene expression during angiosperm diversification accompany the origin and evolution of the flower.
The origin and rapid diversification of the angiosperms (Darwin's "Abominable Mystery") has engaged generations of researchers. Here, we examine the floral genetic programs of phylogenetically pivotal angiosperms (water lily, avocado, California poppy, and Arabidopsis) and a nonflowering seed plant (a cycad) to obtain insight into the origin and subsequent evolution of the flower. Transcriptional cascades with broadly overlapping spatial domains, resembling the hypothesized ancestral gymnosperm program, are deployed across morphologically intergrading organs in water lily and avocado flowers. In contrast, spatially discrete transcriptional programs in distinct floral organs characterize the more recently derived angiosperm lineages represented by California poppy and Arabidopsis. Deep evolutionary conservation in the genetic programs of putatively homologous floral organs traces to those operating in gymnosperm reproductive cones. Female gymnosperm cones and angiosperm carpels share conserved genetic features, which may be associated with the ovule developmental program common to both organs. However, male gymnosperm cones share genetic features with both perianth (sterile attractive and protective) organs and stamens, supporting the evolutionary origin of the floral perianth from the male genetic program of seed plants.


Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and suppression of ERK1/2 MAPK in HeLa cells.
Ursolic acid (UA), a natural pentacyclic triterpenoid compound, has been demonstrated to induce apoptosis in various tumors. The aim of the present study was to elucidate the molecular mechanisms of UA-induced apoptosis in HeLa cells. Here, we reported that UA induced apoptosis through the mitochondrial intrinsic pathway in HeLa cells, as shown by release of cytosol cytochrome c, activation of caspase-9 and -3, reduction of Bcl-2 and Bcl-xL, and increase of Bax and Bak. UA down-regulated the phosphorylation of ERK1/2 and p38, whereas phosphorylation of JNK was unchanged. The roles of ERK1/2 and p38 were further confirmed using the ERK1/2 inhibitor (U0126) and p38 inhibitor (SB203580). U0126 markedly increased UA-induced the Bax/Bcl-2 ratio, the increase of cytosol cytochrome c, and the levels of cleaved caspase-3, but SB203580 had little effects on the above characters, suggesting the ERK1/2 signaling pathway is required for apoptosis. Furthermore, UA up-regulated DUSP 1, 2, 4, 5, 6, 7, 9, and 10 mRNA expressions, which may be a clue for the role of dephosphorylation of ERK1/2 and p38. These data suggested that the apoptotic mechanism of UA treatment in HeLa cells was through the mitochondrial intrinsic pathway and closely associated with the suppression of the ERK1/2 signaling pathway.


Reduction of phase-induced intensity noise in a fiber-based coherent Doppler lidar using polarization control.
Optimization of signal-to-noise ratio is an important aspect in the design of optical heterodyne detection systems such as a coherent Doppler lidar (CDL). In a CDL, optimal performance is achieved when the noise in the detector signal is dominated by local oscillator shot-noise. Most modern CDL systems are built using rugged and cost-efficient fiber optic components. Unfortunately, leakage signals such as residual reflections inherent within fiber components (e.g. circulator) can introduce phase-induced intensity noise (PIIN) to the Doppler spectrum in a CDL. Such excess noise may be a few orders of magnitude above the shot-noise level within the relevant CDL frequency bandwidth--corrupting the measurement of typically weak backscattered signals. In this study, observation of PIIN in a fiber-based CDL with a master-oscillator power-amplifier tapered semiconductor laser source is reported. Furthermore, we experimentally demonstrate what we believe is a newly proposed method using a simple polarization scheme to reduce PIIN by more than an order of magnitude.


Clinical significance and taxonomy of Actinobacillus hominis.
Clinical findings in 36 immunosuppressed patients with lower respiratory tract infection or bacteremia with Actinobacillus hominis are described. Animal contact was only recorded for three patients; nine patients died despite appropriate antimicrobial treatment. Although infections with this microorganism seem to be rare, the fact that 37 of 46 strains characterized in this study have been found in Copenhagen indicates that under-reporting may occur. A. hominis is phenotypically relatively homogeneous but can be difficult to differentiate from other Actinobacillus species unless extensive biochemical testing is performed. Mannose-positive strains of A. hominis are especially difficult to differentiate from A. equuli. Attempts to identify A. hominis by automatic identification systems may lead to misidentifications. Ribotyping and DNA-DNA hybridization data show that A. hominis is a homogeneous species clearly separated from other species within the genus Actinobacillus.


Corynebacterium vaginale (Hemophilus vaginalis) bacteremia: clinical study of 29 cases.
Twenty-nine patients with bacteremia due to Corynebacterium vaginale, an inhabitant of the female genital tract, are described. Four were newborn babies. Nineteen were healthy young women delivered at full term by an operative procedure, cesarean section, or episiotomy. Within 48 hours fever and bacteremia developed. While receiving antibiotics the fever returned to normal, usually within 48 hours. The remaining cases were associated with septic abortion, tubal pregnancy, an intrauterine device, hydatidiform mole, and cellulitis. None of the adults showed evidence of brain abscess, meningitis, or endocarditis. Corynebacterium vaginale is an opportunistic minor pathogen that apparently gains access to the blood stream via an exposed vascular bed rather than as the result of immunosupression.


Hypoxia-related protein expression and its clinicopathologic implication in carcinoma of unknown primary.
Carcinoma of unknown primary (CUP) is a heterogeneous entity with different clinical and histological features. The aim of this study was to investigate the clinicopathological features and expression of proteins associated with carcinogenesis and tumor environment in different histological subtypes of CUP. Sixty-nine cases of CUP were subjected to immunohistochemistry for EGFR, phospho-EGFR, HER-2, phospho-HER-2, p53, ERCC1, RRM1, REDD1, HIF1α, COX-2, GLUT-1, 14-3-3σ, Phospho-mTOR, Phospho-S6, AMPKα1, Phospho-Akt, PDGF-β receptor, and caveolin-1, and fluorescence in situ hybridization for HER-2 gene amplification. Fourteen (20.3%) cases were poorly differentiated carcinoma, 24 (34.8%) were adenocarcinoma (AD), 17 (24.6%) were squamous cell carcinoma (SC), and 14 (20.3%) were undifferentiated carcinoma (UD). AD were mostly carcinomatosis type, while SC and UD were mostly nodal type (p < 0.001). SC showed more frequent EGFR overexpression (p < 0.001) and Glut-1 (p = 0.001). AD (p = 0.001) and carcinomatosis (p < 0.001) types showed shorter overall survival. SCs expressing Glut-1, HIF1α, and COX2 showed a poor prognosis (p = 0.048, 0.029, and 0.042, respectively). CUP shows various clinicopathological features according to the histological subtypes. SC is mainly associated with nodal metastasis in the head and neck, and frequent EGFR overexpression and Glut-1 expression. Glut-1, HIF1α, and COX2 expression in SC is associated with a poor prognosis.


A direct growth effect of growth hormone in rat hindlimb shown by arterial infusion.
We have developed a method for infusing substances into one hindlimb of the rat via the arterial supply. A catheter attached to an osmotic minipump is inserted into the right superior vesical artery and advanced to the junction of the right common iliac artery. This arrangement permits either constant or pulsatile infusion for 7 days. We employed this method to study the direct action of rat growth hormone (rGH) on the proximal tibial epiphysial plate in hypophysectomized rats. Infusion of neither the solvent nor ovine prolactin (2 micrograms X rat-1 X day -1) affected epiphysial plate width compared with control (uninfused) legs. The rGH infused at 0.4 and 2.0 micrograms X rat-1 X day-1 produced dose-related local growth effects that were of similar magnitude with either constant or pulsatile (eight 1-h pulses/day) infusion. However, the higher dose of rGH also resulted in a systemic effect (i.e., epiphysial plate growth in the uninfused limb), and the pulsatile mode produced a greater systemic effect than that produced by constant infusion. Our results indicate that GH can act directly on cartilage in vivo to maintain growth and that its effectiveness is not enhanced by pulsatile delivery. In contrast, the indirect (i.e., systemic) growth effects of the hormone may be enhanced by intermittent infusion. Our infusion system is well suited for studying the direct effect of substances on hindlimb tissues in conscious, unrestrained rats over extended periods.


The rapidly evolving landscape of HCC: Selecting the optimal systemic therapy.
Over the past years, there has been a remarkable advance in the systemic treatment options for advanced HCC. The overall survival has gradually increased over time, with larger benefits for patients with sensitive tumors and preserved liver function, the latter being an essential condition for the delivery of sequential lines of treatment and optimization of clinical outcomes. With the approval of new first-line agents and the introduction of immune checkpoint inhibitor-based therapies, the treatment landscape of advanced HCC is becoming wider than ever. Atezolizumab plus bevacizumab and, more recently, durvalumab plus tremelimumab have entered the clinical practice and are the current standard of care for treatment-naïve patients, surpassing sorafenib and lenvatinib monopoly. As no head-to-head comparisons are available among all the first-line treatment options, the recommendation for the most appropriate choice and sequence is patient-driven and integrates efficacy data with clinical comorbidities, background liver disease, and the safety profile of available drugs. In addition, predictive biomarkers for successful patients' stratification are yet to be available and constitute the focus of ongoing research. The treatment algorithm is likely to become even more complex since systemic therapeutic approaches are now being translated into earlier stages of the disease, with an impact on the evolution of the sequential treatment of HCC patients.


A survey on the management of acute rhinosinusitis among Asian physicians.
Based on the `European Position Paper on Rhinosinusitis and Nasal polyps (EP3OS 2007)`, this study aimed to investigate general practitioners (GPs) and other specialists` understanding when managing patients with acute rhinosinusitis (ARS) in Asia. Among a total of 2662 questionnaires completed, 2524 (94.8%) were valid for analysis. There were 1308 GPs (51.8%), 989 otolaryngologists (39.2%) and 227 paediatricians (9%) from Mainland China, Hong Kong, Indonesia, India, Malaysia, Pakistan, Philippines, Singapore, Thailand and Taiwan. ARS is affecting an estimated 6 - 10% of patients seen in a daily out-patient practice. The EP3OS criteria are well supported by Asian physicians (94.1%). Most physicians (62.7%) agreed that radiological investigation is not needed to diagnose ARS. However, even for mild ARS (common cold), medical treatments were still recommended by 87% of GPs, 83.9% of otolaryngologists, and 70% of paediatricians. The top three first-line treatments prescribed were antihistamines (39.2%), nasal decongestants (33.6%), and antibiotics (29.5%). Antibiotics usage increased as the first line treatment of moderate (45.9%) and severe (60.3%) ARS. ARS is commonly managed by GPs, otolaryngologists, and paediatricians in Asia. However, understanding of the management of ARS needs further improvement to minimize unnecessary use of radiological investigations, overuse of antibiotics, and under use of nasal corticosteroids.


Evaluation of Subclinical Atherosclerosis with Carotid Intima-Media and Epicardial Fat Thickness in Patients with Sarcoidosis.
Since many similar mechanisms may play a role in the pathophysiology of sarcoidosis and atherosclerosis, the risk of subclinical atherosclerosis may be increased in patients with sarcoidosis. The aim of this study was to evaluate known markers of subclinical atherosclerosis, namely epicardial fat thickness (EFT) and carotid intima-media thickness (CIMT) in patients with sarcoidosis. This cross-sectional study included a total of 183 subjects, including 94 patients with sarcoidosis (patient group) and a control group of 89 healthy individuals. Measurements of EFT and CIMT were taken from all subjects and recorded. The groups were compared, and differences were analyzed statistically. EFT was higher in patients than in control subjects (6.42±1.12 mm vs 7.13±1.41 mm, p<0.001). CIMT was higher in patients than in control subjects (0.51±0.02 mm vs 0.52±0.02 mm, p=0.003). EFT and CIMT were found to be higher in patients with sarcoidosis than in healthy people. These results indicate that the risk of subclinical atherosclerosis might be increased in these patients.


A multifactorial analysis of melanoma: III. Prognostic factors in melanoma patients with lymph node metastases (stage II).
Twelve prognostic features of melanoma were examined in a series of 185 patients with nodal metastases (Stage II), who underwent surgical treatment at our institution during the past 20 years. Forty-four per cent of the patients presented with synchronous nodal metastases (substage IIA), 44% of the patients had delayed nodal metastases (substage IIB), and 12% of the patients had nodal metastases from an unknown primary site (substage IIC). The patients with IIB (delayed) metastases had a better overall survival rate than patients with IIA (synchronous) metastases, when calculated from the time of diagnosis. These differences could be explained on the basis of tumor burden at the time of initial diagnosis (microscopic for IIB patients versus macroscopic for IIA patients). Once nodal metastases became evident in IIB patients, their survival rates were the same as for substage IIA patients, when calculated from the onset of nodal metastases. The survival rates for both subgroups was 28% at five years and 15% for ten years. Substage IIC patients (unknown 1 degrees site) had better five-year survival rates (39%), but the sample size was small and the differences were not statistically significant. A multifactorial analysis was used to identify the dominant prognostic variables from among 12 clinical and pathologic parameters. Only two factors were found to independently influence survival rates: 1) the number of metastatic nodes (p = 0.005), and the presence or absence of ulceration (p = 0.0019). Additional factors considered that had either indirect or no influence on survival rates (p > 0.10) were: anatomic location, age, sex, remission duration, substage of disease, tumor thickness, level of invasion, pigmentation, and lymphocyte infiltration. All combinations of nodal metastases were analyzed from survival differences. The combination that showed the greatest differences was one versus two to four versus more than four nodes. Their five-year survival rates were 58%, 27% and 10%, respectively (p < 0.001). Ulceration of the primary cutaneous melanoma was associated with a <15% five-year survival rate, while nonulcerative melanomas had a 30% five-year survival rate (p < 0.001). The combination of ulceration and multiple metastatic nodes had a profound adverse effect on survival rates. While tumor thickness was the most important factor in predicting the risk of nodal metastases in Stage I patients (p < 10(-8)), it had no predictive value on the patient's clinical course once nodal metastases had occurred (p = 0.507). The number of metastatic nodes and the presence of ulceration are important factors to account for when comparing surgical results, and when analyzing the efficacy of adjunctive systemic treatments.


Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism.
A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.


Pseudomonas syringae hijacks plant stress chaperone machinery for virulence.
Plant heat shock protein Hsp70 is the major target of HopI1, a virulence effector of pathogenic Pseudomonas syringae. Hsp70 is essential for the virulence function of HopI1. HopI1 directly binds Hsp70 through its C-terminal J domain and stimulates Hsp70 ATP hydrolysis activity in vitro. In plants, HopI1 forms large complexes in association with Hsp70 and induces and recruits cytosolic Hsp70 to chloroplasts, the site of HopI1 localization. Deletion of a central P/Q-rich repeat region disrupts HopI1 virulence but not Hsp70 interactions or association with chloroplasts. Thus, HopI1 must not only bind Hsp70 through its J domain, but likely actively affects Hsp70 activity and/or specificity. At high temperature, HopI1 is dispensable for P. syringae pathogenicity, unless excess Hsp70 is provided. A working hypothesis is that Hsp70 has a defense-promoting activity(s) that HopI1 or high temperature can subvert. Enhanced susceptibility of Hsp70-depleted plants to nonpathogenic strains of P. syringae supports a defense-promoting role for Hsp70.


Molecular detection of antibiotic resistance: when and where?
Antibiotic resistance is a key issue affecting public health, and diagnostic bacteriology laboratories are essential for prompt recognition of resistant isolates. Determination of susceptibility or resistance using phenotypic tests is a 'gold standard' against which newer technologies are compared in terms of performance, cost and ease of use. Molecular methods for detecting resistance are myriad, and are used widely in academia and in reference laboratories, but gaining a significant foothold in diagnostic laboratories is proving more difficult. However, if used widely in a diagnostic setting, these techniques would impact more directly on patient care and would be valuable infection control tools, e.g. by rapidly confirming patients colonized by resistant bacteria. The cost of molecular assays may be considered prohibitive, and this is compounded by the daunting variety of proprietary platforms available; most diagnostic laboratories would prefer to invest their capital and to train their staff in a single versatile technology. In a market that has no clear leader, many laboratories are understandably reluctant to gamble on making the correct choice. If molecular detection of resistance is to achieve wide acceptance, manufacturers must broaden the repertoires of their technologies, develop more off-the-shelf applications with in-built quality control, and make them suitable for laboratory personnel with no specialist expertise in molecular biology.


[Marfan syndrome and valvular disease].
Marfan syndrome is a hereditary disease of the connective tissue with increased mortality mostly due to changes of the cardiovascular system. We describe our experience with the surgical treatment of 243 patients with Marfan syndrome and cardiovascular complications. We report the results of treatment of annulo-aortal ectasia using the classical surgical methods of Bentall DeBono and Cabrol and the method for preservation of the native aortic valve and concomitant surgery of the mitral valve. Reconstruction or replacement of the mitral valve is mainly based on the classical indications. Preservation of the native aortic valve and reconstruction of the mitral valve in patients with Marfan syndrome is possible but the long-term results are still unknown.


Effectiveness of Stellate Ganglion Block Under Fuoroscopy or Ultrasound Guidance in Upper Extremity CRPS.
Stellate Ganglion Block (SGB) is an effective technique which may be used to manage upper extremities pain due to Chronic Regional Pain Syndrome (CRPS), in this study we tried to evaluate the effectiveness of this procedure under two different guidance for management of this syndrome. The purpose of this study was to evaluate the effectiveness of ultrsound guide SGB by comparing it with the furoscopy guided SGB in upper extermities CRPS patients in reducing pain & dysfuction of the affected link. Fourteen patients with sympathetic CRPS in upper extremities in a randomized method with block randomization divided in two equal groups (with ultrasound or fluoroscopic guidance). First group was blocked under fluoroscopic guidance and second group blocked under ultrasound guidance. After correct positioning of the needle, a mixture of 5 ml bupivacaine 0.25% and 1 mL of triamcinolone was injected. These data represent no meaningful statistical difference between the two groups in terms of the number of pain attacks before the blocks, a borderline correlation between two groups one week and one month after the block and a significant statistical correlation between two groups three month after the block. These data represent no meaningful statistical difference between the patients of any group in terms of the pain intensity (from one week to six months after block), p-value = 0.61. These data represent a meaningful statistical difference among patients of any group and between the two groups in terms of the pain intensity (before the block until six months after block), p-values were 0.001, 0.031 respectively. According the above mentioned data, in comparison with fluoroscopic guidance, stellate ganglion block under ultrasound guidance is a safe and effective method with lower complication and better improvement in patient's disability indexes.


Cefotaxime aminoglycoside interactions.
Minimum inhibitory concentrations and minimum bactericidal concentrations were determined for cefotaxime, gentamicin, tobramycin and amikacin and for the combination of cefotaxime and each of the aminoglycosides in vitro against 200 strains of Enterobacteriaceae. 91% were susceptible to cefotaxime, 93.5% were susceptible to gentamicin, 89.5% were susceptible to amikacin and 68% were susceptible to tobramycin. There were 95 strains which could be evaluated for synergistic killing by the antimicrobial combinations. Synergism was shown against 78% of strains by cefotaxime and amikacin, against 71% by cefotaxime and tobramycin and against 64% by cefotaxime and gentamicin. In 19 of 22 instances where a bacterial strain was resistant to both cefotaxime and the aminoglycoside, synergistic killing with clinically achievable levels of both antimicrobial agents was demonstrated. There was no significant decrease in concentration of any of the three aminoglycosides after incubation with cefotaxime at 37 degrees C for 0, 4 or 24 h.


How to treat myelodysplastic syndrome with clinical features resembling Behçet syndrome: a case-based systematic review.
The association between myelodysplastic syndrome (MDS) and Behçet syndrome (BS) is recognized for over 25 years. High frequency of trisomy 8 and intestinal ulcers are striking features of this association. There are no recommendations for how these patients should be treated. A systematic literature review was performed in PubMed using the keyword combination "(((((intestinal) OR gastrointestinal) OR ulcer) OR Behcet*)) AND ((myelodysplastic syndrome) OR MDS)" in March 2019. Our aim was to gain insight regarding clinical responses to individual treatment modalities. A recent case was also presented and included in the analysis. Data from 41 articles reporting on a total of 53 patients carried adequate information to assess treatment responses. Glucocorticoids provided benefit in 23 of 43 patients. Azacitidine, decitabine, thalidomide, and cyclosporine contributed to a clinical improvement in 4/6, 2/3, 3/4, and 5/8 patients respectively. Hematopoietic stem cell transplantation was successful in 9 of 13 patients. With the use of TNF inhibitors, azathioprine, and mesalamine derivatives, clinical improvement was observed in 3/11, 0/4, and 6/18 patients respectively. Patients with MDS and BS-like features who are resistant to glucocorticoids have so far benefited more from treatment approaches directed at MDS, rather than the immunosuppressive agents used for BS.


Combinations of host biomarkers predict mortality among Ugandan children with severe malaria: a retrospective case-control study.
Severe malaria is a leading cause of childhood mortality in Africa. However, at presentation, it is difficult to predict which children with severe malaria are at greatest risk of death. Dysregulated host inflammatory responses and endothelial activation play central roles in severe malaria pathogenesis. We hypothesized that biomarkers of these processes would accurately predict outcome among children with severe malaria. Plasma was obtained from children with uncomplicated malaria (n = 53), cerebral malaria (n = 44) and severe malarial anemia (n = 59) at time of presentation to hospital in Kampala, Uganda. Levels of angiopoietin-2, von Willebrand Factor (vWF), vWF propeptide, soluble P-selectin, soluble intercellular adhesion molecule-1 (ICAM-1), soluble endoglin, soluble FMS-like tyrosine kinase-1 (Flt-1), soluble Tie-2, C-reactive protein, procalcitonin, 10 kDa interferon gamma-induced protein (IP-10), and soluble triggering receptor expressed on myeloid cells-1 (TREM-1) were determined by ELISA. Receiver operating characteristic (ROC) curve analysis was used to assess predictive accuracy of individual biomarkers. Six biomarkers (angiopoietin-2, soluble ICAM-1, soluble Flt-1, procalcitonin, IP-10, soluble TREM-1) discriminated well between children who survived severe malaria infection and those who subsequently died (area under ROC curve>0.7). Combinational approaches were applied in an attempt to improve accuracy. A biomarker score was developed based on dichotomization and summation of the six biomarkers, resulting in 95.7% (95% CI: 78.1-99.9) sensitivity and 88.8% (79.7-94.7) specificity for predicting death. Similar predictive accuracy was achieved with models comprised of 3 biomarkers. Classification tree analysis generated a 3-marker model with 100% sensitivity and 92.5% specificity (cross-validated misclassification rate: 15.4%, standard error 4.9%). We identified novel host biomarkers of pediatric severe and fatal malaria (soluble TREM-1 and soluble Flt-1) and generated simple biomarker combinations that accurately predicted death in an African pediatric population. While requiring validation in further studies, these results suggest the utility of combinatorial biomarker strategies as prognostic tests for severe malaria.


Restriction endonuclease map of corynebacteriophage omega ctox+ isolated from the Park-Williams no. 8 strain of Corynebacterium diphtheriae.
The toxigenic corynebacteriophage omega tox+ was isolated from the hypertoxigenic Park-Williams no. 8 (PW8) strain of Corynebacterium diphtheriae and compared with the toxigenic corynebacteriophage beta tox+. The physical size and host range of both phages were found to be identical. An endonuclease restriction map of omega tox+ was constructed, and the locations of the cohesive ends (cos), phage attachment site (attP), and the diphtheria tox operon were identified. The genome of omega tox+ was found to differ from that of beta tox+ in three regions. In addition, omega tox+ was shown to be integrated into two nontandem corynebacterial phage attachment sites (attB1, attB2) in the PW8 chromosome. The differences in the restriction endonuclease digestion maps of omega tox+ and beta tox+ and the contribution of double lysogeny are discussed in relation to the hypertoxigenicity of the PW8 strain.


Impact of transient elastography on clinical decision-making in patients with chronic viral hepatitis.
Transient elastography is a noninvasive tool to quantify liver fibrosis by liver stiffness measurements (LSMs). Previous studies have extensively evaluated the accuracy of LSMs compared to liver biopsy. In this retrospective study we explore potential impact of LSMs on clinical decisions in chronic viral hepatitis. LSM-based medical advice whether to start antiviral treatment and/or surveillance for hepatocellular carcinoma (HCC) and clinical follow-up after LSMs were analyzed in 349 patients. In 20% of 184 hepatitis B virus (HBV)-infected patients and 38% of 165 hepatitis C virus (HCV)-infected patients, significant fibrosis (≥F2) was detected. In 5% (n = 7) of the 129 untreated HBV patients and in 12% (n = 19) of the HCV-infected patients, antiviral treatment was recommended solely based on LSMs. Advice for surveillance for HCC was in 40 patients based solely on LSMs (11% of all patients). Furthermore, 95% of 19 non-viremic HCV-patients (after spontaneous clearance or sustained viral response) could be discharged due to favorable LSMs (≤F2). Medical advice was followed by the treating physician in the majority of cases. However, in only 47% of 51 HCV-infected patients with advice to start treatment, this was followed in clinical practice. Transient elastography has a major impact on clinical practice, both as an indication to start or postpone antiviral treatment, to start surveillance for HCC, and to discharge HCV patients from follow-up after viral clearance and favorable LSMs. Medical advice to start antiviral treatment is followed in the large majority of HBV patients, but in only half of HCV patients.


The impact of graphene oxide sheet lateral dimensions on their pharmacokinetic and tissue distribution profiles in mice.
Although the use of graphene and 2-dimensional (2D) materials in biomedicine has been explored for over a decade now, there are still significant knowledge gaps regarding the fate of these materials upon interaction with living systems. Here, the pharmacokinetic profile of graphene oxide (GO) sheets of three different lateral dimensions was studied. The GO materials were functionalized with a PEGylated DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), a radiometal chelating agent for radioisotope attachment for single photon emission computed tomography (SPECT/CT) imaging. Our results revealed that GO materials with three distinct size distributions, large (l-GO-DOTA), small (s-GO-DOTA) and ultra-small (us-GO-DOTA), were sequestered by the spleen and liver. Significant accumulation of the large material (l-GO-DOTA) in the lungs was also observed, unlike the other two materials. Interestingly, there was extensive urinary excretion of all three GO nanomaterials indicating that urinary excretion of these structures was not affected by lateral dimensions. Comparing with previous studies, we believe that the thickness of layered nanomaterials is the predominant factor that governs their excretion rather than lateral size. However, the rate of urinary excretion was affected by lateral size, with large GO excreting at slower rates. This study provides better understanding of 2D materials in vivo behaviour with varying structural features.


[Methods of automated cell analysis and their application in radiation biology].
The present review is concerned with the methods of automated analysis of biological micro-objects and covers two groups into which all the systems of automated analysis can be divided--systems of flow (flow cytometry) and scanning (image analysis systems) type. Particular emphasis has been placed on their use in radiobiological studies, namely, in the micronucleus test, a cytogenetic assay for monitoring the clastogenic action of ionizing radiation commonly used at present. It is evident that the problem is acute, with of radiobiologists' interest in the biological action of low-dose radiation recently increasing. In addition, the estimation of a low-level damage requires the analysis of a large number of experimental objects. Examples of using both the methods elsewhere and actual setups are given. The analysis of advantages and disadvantages of the methods of automated cell analysis enables us to choose more thoroughly between the systems of flow and scanning type to use them in particular research.


Recombinant Lhca2 and Lhca3 subunits of the photosystem I antenna system.
In this study, two gene products (Lhca2 and Lhca3), encoding higher plants (Arabidopsis thaliana) Photosystem I antenna complexes, were overexpressed in bacteria and reconstituted in vitro with purified chloroplast pigments. The chlorophyll-xanthophyll proteins thus obtained were characterized by biochemical and spectroscopic methods. Both complexes were shown to bind 10 chlorophyll (a and b) molecules per polypeptide, Lhca2 having higher chlorophyll b content as compared to Lhca3. The two proteins differed for the number of carotenoid binding sites: two and three for Lhca2 and Lhca3, respectively. beta-carotene was specifically bound to Lhca3 in addition to the xanthophylls violaxanthin and lutein, indicating a peculiar structure of carotenoid binding sites in this protein since it is the only one so far identified with the ability of binding beta-carotene. Analysis of the spectroscopic properties of the two pigment proteins showed the presence of low energy absorption forms (red forms) in both complexes, albeit with different energies and amplitudes. The fluorescence emission maximum at 77 K of Lhca2 was found at 701 nm, while in Lhca3 the major emission was at 725 nm. Reconstitution of Lhca3 without Chl b reveals that Chl b is not involved in originating the low energy absorption forms of this complex. The present data are discussed in comparison to the properties of the recombinant Lhca1 and Lhca4 complexes and of the native LHCI preparation, previously analyzed, thus showing a comprehensive description of the gene products composing the Photosystem I light harvesting system of A. thaliana.