Sonography of Normal and Abnormal Thyroid and Parathyroid Glands.
Ultrasonography (US) represents the most sensitive and efficient method for the evaluation of the thyroid and parathyroid glands. Infectious and autoimmune thyroiditis are common diseases, usually diagnosed and followed up by clinical examination and laboratory analyses. Nevertheless, US plays an important role in confirming diagnoses, predicting outcomes and, in autoimmune hyperthyroidism, in titrating therapy. Conversely, in nodular thyroid disease US is the imaging method of choice for the characterization and surveillance of lesions. It provides consistent clues in predicting the risk of malignancy, thus directing patient referral for fine-needle aspiration (FNA) biopsy. Suspicious US features generally include marked hypoechogenicity, a shape taller than it is wide, ill-defined or irregular borders, microcalcifications and hardness at elastographic evaluation. Finally, the role of US in thyroid cancer is to evaluate extension beyond the thyroid capsule and to assess nodal metastases or tumor recurrence. The main application of US in parathyroid diseases is represented by primary hyperparathyroidism. In this condition, US plays a role after biochemical diagnosis, and it should always be strictly performed for localization purposes. In both thyroidal and parathyroid diseases, US is recommended as a guide in FNA biopsies.


Does stereotype threat influence performance of girls in stereotyped domains? A meta-analysis.
Although the effect of stereotype threat concerning women and mathematics has been subject to various systematic reviews, none of them have been performed on the sub-population of children and adolescents. In this meta-analysis we estimated the effects of stereotype threat on performance of girls on math, science and spatial skills (MSSS) tests. Moreover, we studied publication bias and four moderators: test difficulty, presence of boys, gender equality within countries, and the type of control group that was used in the studies. We selected study samples when the study included girls, samples had a mean age below 18years, the design was (quasi-)experimental, the stereotype threat manipulation was administered between-subjects, and the dependent variable was a MSSS test related to a gender stereotype favoring boys. To analyze the 47 effect sizes, we used random effects and mixed effects models. The estimated mean effect size equaled -0.22 and significantly differed from 0. None of the moderator variables was significant; however, there were several signs for the presence of publication bias. We conclude that publication bias might seriously distort the literature on the effects of stereotype threat among schoolgirls. We propose a large replication study to provide a less biased effect size estimate.


[Adults with congenital heart diseases: a growing population, a multidisciplinary approach].
Untill recently, congenital heart disease was considered as a childhood's disease. With improvement in pediatric survival, adults with a congenital heart disease (ACHD) represent an emerging group of patients who need specialized medical care. In 2010, the ESC published newguidelines on global and specific management of adults with congenital heart disease. ACHD centers organize appropriate medical care for these patients, promote specialist training and national scientific research in collaboration with other national ACHD centers.


Skin cancers amongst four Nigerian albinos.
Albinism is an established risk factor for skin cancer in black Africans, and high levels of ultraviolet radiation increase the risk of the three major forms of skin cancer. We present four albinos with histologic diagnoses of skin cancer who were seen at the University of Calabar Teaching Hospital, Calabar, Nigeria from January 2005 to December 2006. Skin cancer in these cases was compared with the total skin cancer affecting 29 patients during the study period. Twenty-nine patients presented with skin cancer during the study period. Four Nigerian albinos (two men and two women) with skin cancer accounted for 13.8% of the skin cancers observed during the 2-year period. They ranged in age from 22 to 40 years (mean, 27.8 years). The sites of the lesions included the head [squamous cell carcinoma (SCC) in two patients and basal cell carcinoma (BCC) in one patient] and the upper limb (melanoma). All tumors were excised; in addition, patients with SCC and melanoma received adjuvant chemotherapy. Two patients, one woman with SCC and the patient with melanoma, showed residual tumor because of inadequate excision. During the evaluation period between 14 and 18 months, the sites appeared to be healed with no evidence of recurrence in the male with SCC and female with BCC. Albinism and solar radiation are risk factors for skin cancer. Early implementation of public education strategies on prevention should improve outcome.


Foxo3b but not Foxo3a activates cyp19a1a in Epinephelus coioides.
FOXO3 has been shown to be a critical transcription factor for folliculogenesis in mammals, while the information on its roles in reproduction of nonmammalian vertebrates remains scarce. In this study, two foxo3 homologs, namely foxo3a and foxo3b, were identified in a teleost, the orange-spotted grouper Epinephelus coioides. foxo3a was mainly expressed in the central nervous system, ovary, and gut whereas foxo3b was expressed ubiquitously in tissues examined. In contrast to the dominant expression of mammalian FOXO3 in germ cells but barely detectable in ovarian follicular cells, immunoreactive Foxo3a and Foxo3b were identified both in the ovarian germ cells and follicular cells. The immunointensities of both Foxo3a and Foxo3b in ovarian follicular cells during vitellogenesis were significantly increased stage-dependently, and co-localized with Cyp19a1a. In the nucleus of ovarian follicular cells, both Foxo3a and Foxo3b immunostaining could be detected at the vitellogenic stages. Transient transfection and EMSA showed that Foxo3a and Foxo3b upregulated cyp19a1a promoter activities in vitro through a conserved Foxo-binding site, with the latter being a more potent activator. However, ChIP analysis showed that only Foxo3b binds to cyp19a1a proximal promoter region containing the conserved Foxo-binding site in the vitellogenic ovary. Taken together, these results suggested that Foxo3a and Foxo3b are involved in the ovarian development possibly through regulating the ovarian germ cells as well as follicular cells, and Foxo3b but not Foxo3a may activate cyp19a1a in the ovarian follicular cells during vitellogenesis in the orange-spotted grouper.


Accelerating effect of an MRL gene locus on the severity and onset of arthropathy in DBA/1 mice.
To analyze the influence of the genetic background of an arthritis-prone strain of mice, MRL, on the spontaneous development of arthropathy in DBA/1 mice, which histopathologically resembles enthesopathy in humans, and to clarify the strain-specific gene loci and their interactions that confer susceptibility to arthropathy. MRL, DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) intercross mice were prepared, and the severity and onset of arthropathy of the ankle joints in individual mice were quantified (0-3 and 0-5 scale, respectively). A genome-wide scan of 271 male F(2) intercross mice with polymorphic microsatellite markers was performed. Only male DBA/1, (MRL x DBA/1)F(1), and (MRL x DBA/1)F(2) mice developed arthropathy. The macroscopic and histopathologic findings of arthropathy in the F(2) mice were similar to those in the parental DBA/1 mice, but the onset was significantly earlier. In the quantitative trait locus analysis of male F(2) mice, 1 susceptibility locus for both the severity and early onset of the disease in the region of an MRL allele, Amd1, was located at marker D10Mit259 (map position 40.0 cM), which was common to 1 of the sialadenitis susceptibility loci in MRL mice, Asm1. Another susceptibility locus for the severity and early onset of arthropathy in the region of a DBA allele, Amd2, was located at D3Mit46 (29.5 cM). These loci manifested an additive effect on the development of arthropathy. Arthropathy in DBA/1 mice is under the control of an allelic combination of gene loci, one of which is common to the locus for sialadenitis in MRL/MpJ-lpr/lpr mice.


Steep corneal curvature: a fetal alcohol syndrome landmark.
Keratometry was performed on 30 fetal alcohol syndrome (FAS) and fetal alcohol effect (FAE) children. Horizontal keratometric measurements that are 46.00 diopters or greater appear to be an objective landmark of FAS. Keratometry is recommended as a routine test in evaluating suspected FAS children and appears to have value in screening the general school population for FAS.


Transvaal Stromatolite: First Evidence for the Diversification of Cells about 2.2 x 109 Years Ago.
The well-preserved fossil remnants of filamentous blue-green algae have been found in petrographic thin sections of a dolomitic limestone stromatolite in the Transvaal Sequence of South Africa. Some of these filaments contain enlarged cells which are interpreted as akinetes. A new species and genus, Petraphera vivescenticula, is proposed for this microfossil, which is morphologically similar to the living cyanophyte genus Raphidiopsis. This would constitute the first known occurrence of cell diversification in the Precambrian with an age of about 2.2 x 10(9) years.


The Champions League - Improving the quality of in-patient antibiotic prescription in Trauma and Orthopaedics.
A Trust level audit demonstrated that the trauma and orthopaedic department did not reach its own standards in adhering to Trust antibiotic prescribing guidelines. Junior doctors are the main prescribers of antibiotics during inpatient stays. Local policy states that for all inpatients on antibiotics, the start date, duration, and indication for antibiotics must be documented on the drug card. Each patient drug card was reviewed by the department pharmacist and it was recorded whether the documentation was in line with Trust policy. A monthly league table, coined 'The Champions League', was created. It was published monthly and displayed in the doctors' office and other clinical areas to highlight which doctors had or had not adhered to the prescribing guidelines. In August 2012 the monthly audit for the trauma and orthopaedic department included 74 patients. The total number of antibiotic courses prescribed was 28; of these courses only 15 (53.5%) had an indication documented and 15 (53.5%) had a review/stop date documented. In December 2012, after two published league tables, 61 patients were reviewed. A total of 19 antibiotic courses were prescribed; 18 (94.7%) had the indication documented and 16 (84.2%) had the review/stop date documented. The standards of prescribing improved within the department and good prescribing practice became ingrained into each doctor's practice. The league table proved to be a novel tool that helped to raise the profile of antibiotic prescribing and change doctor prescribing habits. It created a competitive spirit within the department which improved morale. Doctors responded positively to feedback if they were not achieving the desirable standards, and enjoyed the challenge of improving the standard of prescribing.


[Correction of a diabetes mellitus type 1 on primate with encapsulated islet of pig pancreatic transplant].
The allogeneic transplantation of pancreatic islet cells into diabetic patients is severely restricted by the recurrent lack of organs. To the lack of donors is added the fact that several pancreas donors are often needed in order to treat a single diabetic recipient. Another source of cells that can produce insulin would therefore be of major interest. The pig constitutes a possible option to be taken seriously. Nonetheless, grafting pig islets might prove difficult because of the species barrier. The principal obstacle to the xenotransplantation of cells remains the necessity for powerful immunosuppression, probably inapplicable in man. Therefore, we have centred our work around the encapsulation of islets in order to evaluate the possibility of using pig cells without immunosuppression. (1) This experimental work first evaluated the influence of the age of the pig (young versus adult pigs) on the size of the islets, the collagen and the vascular structures. Adult donor pigs were selected. (Dufrane et al., Pancreas 30(2), 2005). (2) After deciding on the age, all the parameters involved in the removal of the pancreas and the procedures of isolating the pig islets were scrutinized by multivariable analysis. (Dufrane et al., Xenotransplantation 13(3), 2006). (3) Before evaluating the effect of encapsulation on the pig islets in diabetic monkeys, the biocompatibility of an alginate membrane was first evaluated in a non-diabetic primate model without immunosuppression. The long term stability and biocompatibility of pig islets encapsulated in alginate have been confirmed for up to six months after implantation under the renal capsule. A small proportion of these encapsulated pig islets not only survived for six months but remained capable of reacting in vitro to stimulation with glucose + forskolin, thus demonstrating preserved endocrine function. This in vivo experience has enabled us to identify the most important parameters for successful encapsulation. (Dufrane et al., Transplantation 81(9), 2006; Dufrane et al., Biomaterials 27(17), 2005). We then (4) investigated the most appropriate means of inducing irreversible diabetes in primates: a low dose (50 mg/kg) of streptozotocine (STZ) permanently destroys more than 97% of the insulin-producing cells of the pancreas, without any side effects on hepatic or renal function. (Dufrane et al., Transplantation 81(1), 2006 (5) After induction of diabetes by STZ in primates, the capacity of encapsulated pig islets to control diabetes after transplantation was evaluated both under the renal capsule and in the form of a graft of a monolayer of cells in the subcutaneous space. The second technique enabled the diabetic status to be controlled for at least six months without any immunosuppression in four primates. This result is unique since only major immunosuppressant regimes have so far brought comparable results.


Antioxidant and enzymatic responses to oxidative stress induced by cold temperature storage and ripening in mango (Mangifera indica L. cv. 'Cogshall') in relation to carotenoid content.
The effects of 15 days of storage at 12 °C and 7 °C followed by fruit ripening at 20 °C on oxidative status, antioxidant defense systems and carotenoid accumulation were studied for two successive years in mango fruits (Mangifera indica L.) cv. Cogshall. Changes in the non-enzymatic (ascorbate) and enzymatic (SOD, CAT, APX, MDHAR, DHAR and GR) antioxidant systems, as well as oxidative parameters (H2O2 and MDA) and the contents of the major carotenoids were measured for three maturity stages, at harvest and after ripening following cold temperature storage. In control conditions (20 °C), ripening induced an increase in oxidation resulting in ROS production and a decrease in ascorbate content. Fruit tissue protection was activated by means of antioxidant and ascorbate regeneration enzyme systems. Carotenoid accumulated exponentially during ripening. Storage at low temperatures increased respiration crisis intensity and therefore increased oxidation in the fruit pulp. Fruit response to this increase varied according to the maturity stage, i.e., enzymatic responses in younger fruits were very low in comparison to the control, whereas second harvest fruits had a significantly higher degree of enzymatic activity to cope with the oxidative stress. Carotenoid contents decreased with low temperatures and first harvest fruits showed significantly lower values than the control, in opposition to second harvest fruits that appeared not to be affected. We also suggest that, based on a review of the literature, a link can be made between antioxidant system defense and carotenoid metabolism since ROS seems to play a central role as a stress signal in plants.


MR-guidance in clinical reality: current treatment challenges and future perspectives.
Magnetic Resonance-guided radiotherapy (MRgRT) marks the beginning of a new era. MR is a versatile and suitable imaging modality for radiotherapy, as it enables direct visualization of the tumor and the surrounding organs at risk. Moreover, MRgRT provides real-time imaging to characterize and eventually track anatomical motion. Nevertheless, the successful translation of new technologies into clinical practice remains challenging. To date, the initial availability of next-generation hybrid MR-linac (MRL) systems is still limited and therefore, the focus of the present preview was on the initial applicability in current clinical practice and on future perspectives of this new technology for different treatment sites.MRgRT can be considered a groundbreaking new technology that is capable of creating new perspectives towards an individualized, patient-oriented planning and treatment approach, especially due to the ability to use daily online adaptation strategies. Furthermore, MRL systems overcome the limitations of conventional image-guided radiotherapy, especially in soft tissue, where target and organs at risk need accurate definition. Nevertheless, some concerns remain regarding the additional time needed to re-optimize dose distributions online, the reliability of the gating and tracking procedures and the interpretation of functional MR imaging markers and their potential changes during the course of treatment. Due to its continuous technological improvement and rapid clinical large-scale application in several anatomical settings, further studies may confirm the potential disruptive role of MRgRT in the evolving oncological environment.


Prophylactic Vaccine Targeting TLR3 on Dendritic Cells Ameliorates Eosinophilic Pneumonia in a Mouse SARS-CoV Infection Model.
Putative subcomponent vaccines of severe acute respiratory syndrome coronavirus spike protein and ARNAX (TLR3-specific adjuvant for priming dendritic cells) were examined and compared with spike protein + Alum in a mouse BALB/c model. Survival, body weight, virus-neutralizing Ab titer in the blood, and viral titer in the lung were evaluated for prognosis markers. The infiltration degrees of eosinophils in the lung were histopathologically monitored at 10 d postinfection. The results were: (1) adjuvant was essential in vaccines to achieve a complete recovery from infection, (2) ARNAX displayed optimal body weight recovery compared with Alum, (3) ARNAX was optimal for the amelioration of eosinophilic pneumonia, and (4) the eosinophil infiltration score was not associated with the neutralizing Ab titer in the blood or viral titer in the lung. Although the pathological link between the TLR3 vaccine and lung eosinophil infiltration remains unclear, severe acute respiratory syndrome-mediated eosinophilic pneumonia can be blocked by the prior induction of dendritic cell priming by ARNAX.


Patients' Opinions on Genetic Counseling on the Increased Risk of Parkinson Disease among Gaucher Disease Carriers.
Gaucher disease (GD) is an autosomal recessive disease caused by GBA mutations that is especially common in the Ashkenazi Jewish (AJ) population. The link between GBA mutations and Parkinson disease (PD), a later-onset neurodegenerative condition, is well established, and studies have shown that GBA carriers have an increased lifetime risk of developing PD. Carrier screening for GD is frequently offered to couples during or prior to pregnancy, especially to those of AJ descent. However, no studies have been performed to assess if prospective parents would want to learn about their risk of developing PD incidentally through carrier screening. It is also unknown if pre-test counseling on this topic would affect screening uptake. In order to answer these questions, a survey was administered to individuals who screened negative for GBA mutations. Of the 75 participants, 86.7% believed that patients should be informed about the increased risk of PD prior to having GD carrier screening, and 93.3% responded that this information would not have changed their decision to have carrier screening. These results indicate that healthcare providers should take into consideration patient preferences when determining how to counsel about GD carrier screening. Additionally, these results have implications for genetic counseling about other later-onset conditions that may be incidentally ascertained through carrier screening.


Combining Decision Rules from Classification Tree Models and Expert Assessment to Estimate Occupational Exposure to Diesel Exhaust for a Case-Control Study.
To efficiently and reproducibly assess occupational diesel exhaust exposure in a Spanish case-control study, we examined the utility of applying decision rules that had been extracted from expert estimates and questionnaire response patterns using classification tree (CT) models from a similar US study. First, previously extracted CT decision rules were used to obtain initial ordinal (0-3) estimates of the probability, intensity, and frequency of occupational exposure to diesel exhaust for the 10 182 jobs reported in a Spanish case-control study of bladder cancer. Second, two experts reviewed the CT estimates for 350 jobs randomly selected from strata based on each CT rule's agreement with the expert ratings in the original study [agreement rate, from 0 (no agreement) to 1 (perfect agreement)]. Their agreement with each other and with the CT estimates was calculated using weighted kappa (κ w) and guided our choice of jobs for subsequent expert review. Third, an expert review comprised all jobs with lower confidence (low-to-moderate agreement rates or discordant assignments, n = 931) and a subset of jobs with a moderate to high CT probability rating and with moderately high agreement rates (n = 511). Logistic regression was used to examine the likelihood that an expert provided a different estimate than the CT estimate based on the CT rule agreement rates, the CT ordinal rating, and the availability of a module with diesel-related questions. Agreement between estimates made by two experts and between estimates made by each of the experts and the CT estimates was very high for jobs with estimates that were determined by rules with high CT agreement rates (κ w: 0.81-0.90). For jobs with estimates based on rules with lower agreement rates, moderate agreement was observed between the two experts (κ w: 0.42-0.67) and poor-to-moderate agreement was observed between the experts and the CT estimates (κ w: 0.09-0.57). In total, the expert review of 1442 jobs changed 156 probability estimates, 128 intensity estimates, and 614 frequency estimates. The expert was more likely to provide a different estimate when the CT rule agreement rate was <0.8, when the CT ordinal ratings were low to moderate, or when a module with diesel questions was available. Our reliability assessment provided important insight into where to prioritize additional expert review; as a result, only 14% of the jobs underwent expert review, substantially reducing the exposure assessment burden. Overall, we found that we could efficiently, reproducibly, and reliably apply CT decision rules from one study to assess exposure in another study.


Phytotherapy versus hormonal therapy for postmenopausal bone loss: a meta-analysis.
This meta-analysis included 14 randomized controlled trials involving 780 patients to compare phytotherapy with hormonal therapy in the treatment of postmenopausal bone loss. Current evidence suggests that phytotherapy may possess a similar effect on bone mineral density (BMD) values but clinically is not associated with a high incidence of uterine bleeding and breast pain as is hormonal therapy. Clinical trials indicate that phytotherapy may be a potential treatment for postmenopausal osteoporosis. The objective of this meta-analysis was to compare the efficacy and safety of phytotherapy with that of hormonal therapy, to assess the quality of phytotherapy trials, and to identify herbs used commonly in the treatment of postmenopausal bone loss. A total of 43 electronic databases were searched. The quality of eligible trials was assessed using Jadad's scale. Outcome measures were BMD values and adverse events. Revman 5.0 software was used for data syntheses and meta-analyses. The database search revealed 14 randomized controlled trials involving 780 patients that met the inclusion criteria, and four trials were graded as high quality (score 3-5). There was no significant difference in lumbar, femoral or forearm BMD values between subjects treated with phytotherapy and those treated with hormonal therapy (P>0.05), but the incidence of uterine bleeding and breast pain was significantly lower in those treated with phytotherapy than in those treated with hormonal therapy (P = 0.002 and P = 0.01). The six most commonly used herbs in the included trials were identified. Phytotherapy may not show effects beyond hormonal therapy, but may be safer than hormonal therapy in the treatment of postmenopausal bone loss. Further trials with high-quality study designs should be conducted in this field.


Antinociceptive effect of intracerebroventricularly administered histamine in rats.
Intracerebroventricularly (icv) administered histamine produced a dose-related antinociceptive effect in rats, using the rat tail-hot wire technique as the experimental parameter. The H1-receptor agonist, 2-methyl-histamine, given icv, also induced marked antinociception, whereas the H2-receptor agonist, 4-methylhistamine, produced relatively weaker and transient antinociception. Histamine-induced antinociception was significantly inhibited by mepyramine, a H1-receptor antagonist, but not by cimetidine, a H2-receptor antagonist. 5,6-Dihydroxytryptamine, a specific serotonin neuronolytic agent, and p-chlorophenylalanine, which selectively inhibits serotonin synthesis, markedly inhibited the antinociceptive effect of histamine, which was also attenuated by naloxone, an antagonist for endogenous opioid receptors, and by dexamethasone, which is known to reduce central endorphin concentrations. On the contrary, the effect of histamine was potentiated by adrenalectomy and by metyrapone, an inhibitor of endogenous corticoid synthesis, which are known to enhance central endorphins.


Comparative genomic analysis of clinical Enterococcus faecalis distinguishes strains isolated from the bladder.
Enterococcus faecalis is the most commonly isolated enterococcal species in clinical infection. This bacterium is notorious for its ability to share genetic content within and outside of its species. With this increased proficiency for horizontal gene transfer, tremendous genomic diversity within this species has been identified. Many researchers have hypothesized E. faecalis exhibits niche adaptation to establish infections or colonize various parts of the human body. Here, we hypothesize that E. faecalis strains isolated from the human bladder will carry unique genomic content compared to clinical strains isolated from other sources. This analysis includes comparison of 111 E. faecalis genomes isolated from bladder, urogenital, blood, and fecal samples. Phylogenomic comparison shows no association between isolation source and lineage; however, accessory genome comparison differentiates blood and bladder genomes. Further gene enrichment analysis identifies gene functions, virulence factors, antibiotic resistance genes, and plasmid-associated genes that are enriched or rare in bladder genomes compared to urogenital, blood, and fecal genomes. Using these findings as training data and 682 publicly available genomes as test data, machine learning classifiers successfully distinguished between bladder and non-bladder strains with high accuracy. Genes identified as important for this differentiation were often related to transposable elements and phage, including 3 prophage species found almost exclusively in bladder and urogenital genomes. E. faecalis strains isolated from the bladder contain unique genomic content when compared to strains isolated from other body sites. This genomic diversity is most likely due to horizontal gene transfer, as evidenced by lack of phylogenomic clustering and enrichment of transposable elements and prophages. Investigation into how these enriched genes influence host-microbe interactions may elucidate gene functions required for successful bladder colonization and disease establishment.


Impact of thermal desorption tubes on the variability of exhaled breath data.
Due to the overall low abundance of volatile compounds in exhaled breath, it is necessary to preconcentrate the sample prior to traditional thermal desorption gas chromatography mass spectrometry (TD-GC-MS) analysis. While certain aspects of thermal desorption tubes, such as volatile storage, have been evaluated, many aspects remain uncharacterized. Two common thermal desorption tubes, Tenax TA and Biomonitoring 5TD tubes, were evaluated for background content and flow rate variability. The data illustrate that the Biomonitoring 5TD tubes have the highest number (23) and abundance of background contamination greater than 3x the mean noise when compared to Tenax TA (13) and empty tubes (9). Tentative identifications of the compounds in the background contamination experiment show that greater than 59% (16/27) of the compounds identified have been reported in the breath literature. The data illustrate the TD tube background abundance could account for more than 70% of the chromatographic signal from exhaled breath for these select compounds. Flow rate measurements of 200 Tenax TA and 200 Biomonitoring 5TD tubes show a large range in measured flow rates among the TD tubes (Tenax: 252.9-284.0mL min-1, 5TD: 220.6-255.1mL min-1). Finally, TD tubes of each type, Tenax TA and Biomonitoring 5TD, previously established to have high, medium, and low flow rates, show insignificant differences (p>0.05) among the tubes of different flow rates, using both gas standards and an exhaled breath from a peppermint experiment. Collectively, these results establish overall background compounds attributed to each TD tube type tested. Additionally, while measured flow rate variability is present and plausibly impacts exhaled breath results, the data demonstrate no statistically significant difference was observed between tubes showing high, medium, and low flow rates from two separate sample types.


Two cognitive transitions underlying the capacity for cultural evolution.
This paper proposes that the distinctively human capacity for cumulative, adaptive, open-ended cultural evolution came about through two temporally-distinct cognitive transitions. First, the origin of Homo-specific culture over two MYA was made possible by the onset of a finer-grained associative memory that allowed episodes to be encoded in greater detail. This in turn meant more overlap amongst the distributed representations of these episodes, such that they could more readily evoke one another through self-triggered recall (STR). STR enabled representational redescription, the chaining of thoughts and actions, and the capacity for a stream of thought. Second, fully cognitive modernity following the appearance of anatomical modernity after 200,000 BP, was made possible by the onset of contextual focus (CF): the ability to shift between an explicit convergent mode conducive to logic and refinement of ideas, and an implicit divergent mode conducive to free-association, viewing situations from radically new perspectives, concept combination, analogical thinking, and insight. This paved the way for an integrated, creative internal network of understandings, and behavioral modernity. We discuss feasible neural mechanisms for this two-stage proposal, and outline how STR and CF differ from other proposals. We provide computational evidence for the proposal obtained with an agent-based model of cultural evolution in which agents invent ideas for actions and imitate the fittest of their neighbors' actions. Mean fitness and diversity of actions across the artificial society increased with STR, and even more so with CF, but CF was only effective if STR was already in place. CF was most effective following a change in task, which supports its hypothesized role in escaping mental fixation. The proposal is discussed in the context of transition theory in the life sciences.


Utility of digitally assisted vitreoretinal surgery systems (DAVS) for high-volume vitreoretinal surgery centre: a pilot study.
To compare the surgical experience and preferred imaging platform, between digitally assisted vitreoretinal surgery systems (DAVS) and analogue microscope (AM), for performing various surgical manoeuvres. A questionnaire was used to evaluate the experience of surgeons who used DAVS for at least 6 months in the last 1 year. Twenty-three surgeons, including 12 fellows, answered the questionnaire. Eighty-two per cent of surgeons got accustomed to DAVS in <10 surgeries. The higher magnification provided by DAVS was perceived as helpful by 87.0% surgeons. Seventy-eight per cent surgeons felt that DAVS provided a bigger field of view. Colours displayed on DAVS appeared unnatural to 39.1%. Difficulty using three-dimensional glasses over spectacles, asthenopia and dry eye symptoms while using DAVS were faced by 17.4%, 17.4% and 21.7% surgeons, respectively. Difficulty in frequent switching between DAVS and AM was faced by 30.4% surgeons. Difficulty in depth perception, hand-eye coordination and performance anxiety while using DAVS was faced by 43.5%, 21.7 % and 30.4 % surgeons, respectively. Majority consultants did not have any imaging platform preference for most posterior segment procedures, while majority fellows preferred DAVS. Majority surgeons preferred AM for anterior segment procedures and complicated situations like small pupil, corneal oedema and surgical surprise(s). Once the surgeons became accustomed to DAVS, none of them had to shift back to AM during any case. It was easy to adapt to DAVS. DAVS was preferred for performing most posterior segment surgeries. Drawbacks like unnatural colours of the projected image and difficulty in performing anterior segment manoeuvres need to be addressed.


The Neuro-Mechanical Processes That Underlie Goal-Directed Medio-Lateral APA during Gait Initiation.
Gait initiation (GI) involves passing from bipedal to unipedal stance. It requires a rapid movement of the center of foot pressure (CoP) towards the future swing foot and of the center of mass (CoM) in the direction of the stance foot prior to the incoming step. This anticipatory postural adjustment (APA) allows disengaging the swing leg from the ground and establishing favorable conditions for stepping. This study aimed to describe the neuro-mechanical process that underlies the goal-directed medio-lateral (ML) APA. We hypothesized that controlled knee flexion of the stance leg contributes to the initial ML displacement of the CoP and to the calibration of the first step. Fourteen subjects initiated gait starting from three different initial stance widths of 15 cm (Small), 30 cm (Medium), and 45 cm (Large). Optoelectronic, force platform and electromyogram (EMG) measurements were performed. During APA, soleus activity diminished bilaterally, while tibialis anterior (TA) activity increased, more so in the stance leg than in the swing leg, and to a larger extent with increasing initial stance width. Knee flexion of the stance leg was observed during APA and correlated with the ML CoP displacement towards the swing leg. ML CoP and CoM displacements during APA increased with increasing stance width. The activity of stance-leg TA was correlated with the degree of knee flexion. Swing-leg tensor fasciae latae (TFL) was also active during APA. Across subjects, when stance-leg tibialis activity was low, TFL activity was large and vice versa. The modulation of the ML CoP position during APA allowed the gravity-driven torque to place the CoM just lateral to the stance foot during step execution. Accordingly, the gravity-driven torque, the ML CoM velocity during step execution, and the step width at foot contact (FC) were lower in the Small and greater in the Large condition. Consequently, the position of the stepping foot at FC remained close to the sagittal plane in all three conditions. Conclusively, coordinated activation of hip abductors and ankle dorsiflexors during APA displaces the CoP towards the swing leg, and sets the contact position for the swing foot.


Bedwetting, behaviour and self-esteem: a review of the literature.
The aim of this review was to examine the empirical evidence on the impact of bedwetting and its treatment on a child's self-esteem and behaviour. The inclusion criteria for this review were empirical studies conducted on children, aged 5-16 years old, with primary nocturnal enuresis using measures of self-esteem or behaviour. Studies utilizing psychological measurement scales completed by children were the main focus although those that used scales completed by parents were also included. The electronic databases from 1981 to 1999 were searched, and hand searching of the literature dating back to 1973 was conducted using the reference lists of key papers. Fifteen empirical studies matched the inclusion criteria. There was only one randomised-controlled trial and the rest of the studies were cohort, case-control or cross-sectional design. Evidence of sample bias predominantly due to the use hospital-based and/or 'volunteer' subjects was found in five studies. A further five studies used birth cohort data, which excludes important variables such as the impact of treatment. Four studies used single parent-reported measures, which may under or over-estimate the problem. No large cohort studies were available which compare the self-esteem of bedwetting children with matched controls. The most interesting line of enquiry is pursued by studies looking at whether self-esteem improves with successful treatment. However, the use of self-selected subject groups does not make the current evidence convincing and more work is required to determine outcomes for all children. There is empirical evidence for increased behavioural problems in bedwetting children. Studies conducted on younger children report less behavioural problems with more reported in studies conducted on older children with complex wetting disorders. This may point towards wetting being the primary problem, but more work is needed, as causation in any direction is difficult to ascertain from the literature.


Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease.
Colorectal bacteria may play a role in the pathogenesis of inflammatory bowel disease (IBD). To test the hypothesis that, in affected patients, the numbers of potentially protective mucosal bacteria might be reduced and pathogenic species increased, we compared rectal mucosa-associated flora in patients with IBD and normal controls. Snap-frozen rectal biopsies taken at routine diagnostic colonoscopy from 33 patients with ulcerative colitis, 6 patients with Crohn's disease, and 14 controls with normal colonoscopy were processed, and individual bacterial groups were counted using fluorescent in situ hybridization. Bacteria were mostly found apposed to the epithelial surface and within crypts. Epithelium-associated counts of bifidobacteria in active [median 15/mm of epithelial surface (range, 4-56), n = 14] and quiescent ulcerative colitis [26/mm (range, 11-140), n = 19] were lower than in controls [56/mm (range, 0-144), n = 14; P = 0.006 and P = 0.03, respectively]. Conversely, epithelium-associated Escherichia coli counts were higher in active [82/mm (range, 56-136)] than inactive ulcerative colitis [6/mm (range, 0-136), P = 0.0001] or controls [0/mm (range, 0-16), P < 0.0001]. Epithelium-associated clostridia counts were also higher in active [3/mm (range, 0-9)] than inactive colitis [0/mm (range, 0-9), P = 0.03] or controls [0/mm (range, 0-1); P = 0.0007]. Epithelium-associated E. coli counts were higher in Crohn's disease [42/mm (range, 3-90), n = 6] than controls (P = 0.0006). E. coli were also found as individual bacteria and in clusters in the lamina propria in ulcerative colitis and Crohn's disease but in none of the controls (P < 0.01). Numbers of Lactobacillus and Bacteroides showed no differences between patient groups. The reduction in mucosa-associated bifidobacteria and increase in E. coli and clostridia in patients with IBD supports the hypothesis that an imbalance between potentially beneficial and pathogenic bacteria may contribute to its pathogenesis.


Testing of Lagrange multiplier damped least-squares control algorithm for woofer-tweeter adaptive optics.
A Lagrange multiplier-based damped least-squares control algorithm for woofer-tweeter (W-T) dual deformable-mirror (DM) adaptive optics (AO) is tested with a breadboard system. We show that the algorithm can complementarily command the two DMs to correct wavefront aberrations within a single optimization process: the woofer DM correcting the high-stroke, low-order aberrations, and the tweeter DM correcting the low-stroke, high-order aberrations. The optimal damping factor for a DM is found to be the median of the eigenvalue spectrum of the influence matrix of that DM. Wavefront control accuracy is maximized with the optimized control parameters. For the breadboard system, the residual wavefront error can be controlled to the precision of 0.03 μm in root mean square. The W-T dual-DM AO has applications in both ophthalmology and astronomy.


Prescribing and dispensing practices for oral iron tablets: a Canadian experience.
The formulation of an oral iron tablet may influence its therapeutic efficacy in correcting iron deficiency. In order to determine the oral iron preparations patients in a Canadian urban center were receiving, a questionnaire was circulated to family physicians, internists, surgeons, and obstetrician-gynecologists to determine their prescribing practices. A survey of pharmacies in the city was also conducted to determine which brand of each iron salt (sulfate, gluconate, fumarate) they dispensed for a generic oral iron prescription. Most physicians (74 percent) chose ferrous sulfate as their drug of first choice. The majority of prescribers would not specifically request either enteric-coated/slow-release or nonenteric-coated preparations as first or second choices (71 and 64 percent, respectively). Enteric-coated or slow-release preparations were specified by 10 and 19 percent of physicians as first and second choices, respectively. Most pharmacies (96 percent) dispensed an enteric-coated preparation of ferrous sulfate for a generic prescription. We believe that many patients are receiving iron tablets with altered release properties (enteric-coated/slow-release). These tablets may fail to provide the desired therapeutic benefit based on the known physiology of iron absorption.


Prevalence and Risk Factors for Pulmonary Conditions among Farmers and Ranchers in the Central United States.
This study was conducted to evaluate the prevalence and risk factors for work-related respiratory conditions (asthma, farmer's lung, sinusitis, rhinitis, and environmental allergies, diagnosed by a physician) among farm and ranch operators in the central US. A survey was conducted by the Central States Center for Agricultural Safety and Health (CS-CASH) in 2018, focusing on work-related injuries, illnesses, exposures, and preventive measures in a seven-state region (Iowa, Kansas, Minnesota, Missouri, Nebraska, North Dakota, and South Dakota). Farms and ranches (n = 16,818) with an email address and annual sales exceeding $5,000 were randomly selected for the survey. Agricultural production and weather data were merged with survey responses. The relationship between exposures and respiratory conditions was analyzed using generalized estimating equations. We received responses from 3,268 agricultural operations (19% response rate) containing information on 4,064 individual operators. The life-time prevalence of (any) respiratory conditions among farm/ranch operators was 18%. Risk factors for respiratory conditions included exposures to grain/hay/feed dust (OR 2.41), animal confinement dust (OR 1.57), field/road dust (OR 2.11), manure/silage gasses (OR 1.66), anhydrous ammonia (OR 1.51), fuels/solvents/paints (OR 1.92), older age group >70 vs. <43 (OR 1.40), female gender (OR 1.82), and being primary vs. third operator (OR 1.61). Farmers and ranchers have a high prevalence of respiratory conditions associated with dust and gas exposures at work. More effective protective measures are needed using the hierarchy of controls, including improved use of respiratory protection.


Plasma isoflavone concentrations are not associated with gastric cancer risk among Japanese men and women.
The incidence of gastric cancer throughout the world is ~2-3 times higher in men than in women. Previous research suggested that isoflavones, which are structurally similar to 17β-estradiol, may prevent gastric cancer. Based on a large, population-based, prospective study, we recently reported a null association between dietary isoflavone intake and gastric cancer. However, epidemiologic studies using blood concentrations of isoflavones might better reflect the effect of isoflavones on gastric cancer carcinogenesis than dietary assessment. We therefore conducted a nested case-control study within the Japan Public Health Center-Based Prospective Study. Participants were followed-up from 1990 to 2004. Among 36,745 participants who answered the baseline questionnaire and provided blood samples, 483 gastric cancer cases matched to 483 controls were used in the analysis. ORs and 95% CIs were estimated with a conditional logistic regression model. The overall distribution of plasma isoflavone concentrations was not associated with the development of gastric cancer. Compared with groups with the lowest plasma concentrations (reference groups), the groups with the highest daidzein and genistein concentrations had adjusted ORs and 95% CIs of 1.11 (0.74-1.66; P-trend = 0.6) and 0.96 (0.64-1.44; P-trend = 0.9), respectively. The results did not change when analysis was based on sex, subsite, or histological type. We found no association of plasma isoflavone concentrations with gastric cancer risk. Our data support the previously observed null association between isoflavone intake and gastric cancer risk.


Physiological responses to cold exposure in men: a disabled submarine study.
A disabled submarine (DISSUB) lacking power and/or environmental control will become cold, and the ambient air may become hypercapnic and hypoxic. This study examined if the combination of hypoxia, hypercapnia, and cold exposure would adversely affect thermoregulatory responses to acute cold exposure in survivors awaiting rescue. Seven male submariners (33 +/- 6 yrs) completed a series of cold-air tests (CAT) that consisted of 20-min at T(air) = 22 degrees C, followed by a linear decline (1 degrees C x min(-1)) in T(air) to 12 degrees C, which was then held constant for an additional 150-min. CAT were performed under normoxic, normocapnic conditions (D0), acute hypoxia (D1, 16.75% O2), after 4 days of chronic hypoxia, hypercapnia and cold (D5, 16.75% O2, 2.5% CO2, 4 degrees C), and hypoxia-only again (D8, 16.75% O2). The deltaTsk during CAT was larger (P < 0.05) on D0 (-5.2 degrees C), vs. D1 (-4.8 degrees C), D5 (-4.5 degrees C), and D8 (-4.4 degrees C). The change (relative to 0-min) in metabolic heat production (deltaM) at 20-min of CAT was lower (P < 0.05) on D1, D5, and D8, vs. D0, with no differences between D1, D5 and D8. DeltaM was not different among trials at any time point after 20-min. The mean body temperature threshold for the onset of shivering was lower on D1 (35.08 degrees C), D5 (34.85 degrees C), and D8 (34.69 degrees C), compared to D0 (36.01 degrees C). Changes in heat storage did not differ among trials and rectal temperature was not different in D0 vs. D1, D5, and D8. Thus, mild hypoxia (16.75% F1O2) impairs vasoconstrictor and initial shivering responses, but the addition of elevated F1CO2 and cold had no further effect. These thermoregulatory effector changes do not increase the risk for hypothermia in DISSUB survivors who are adequately clothed.


[Epidemiology of cerebrovascular accidents in the city of Salvador: clinical aspects].
The major clinical findings of acute cerebrovascular accidents (CVA) were analyzed for 1089 patients from Salvador City (Bahia, Brazil) who attended to medical services from 1 July 1979 to 30 June 1980. Data were collected from all hospitals and emergency services, from private and public sectors, which admitted patients with CVA. Hemiplegies and speech disturbances were the most commonly observed findings in both sexes. In 167 patients (23.03%) a reference to an early episode of CVA was found; 34.93% of the patients were in coma at the time of admission and the lethality rate in this group was 80.87%. The quality of the medical attention provided to these patients was commented. A better organization of the services for tertiary prevention is needed in order to improve patient's adhesion and quality of life.


The acid tolerance response of Salmonella typhimurium provides protection against organic acids.
Salmonella typhimurium encounters a variety of acid stress situations during pathogenesis and in the natural environment. These include the extreme low pH encountered in the stomach and a less acidic intestinal environment containing large amounts of organic weak acids (volatile fatty acids). The acid tolerance response (ATR) is a complex defence system that can minimize the lethal effects of extreme low pH (pH3). The data presented illustrate that the ATR can also defend against weak acids such as butyric, acetic or propionic acids. Although an acid shock of pH 4.4 induced the ATR, growth in subinhibitory concentrations of weak acids did not. Various mutations shown to affect tolerance to extreme acid conditions (pH 3) were tested for their effects on tolerance to weak acids. An rpoS mutant lacking the alternative sigma factor sigma s failed to protect cells against weak acids as well as extreme acid pH. The fur (ferric uptake regulator) and atp (Mg(2+)-dependent ATPase) mutants defective in extreme acid tolerance showed no defects in their tolerance to weak acids. Curiously, the atbR mutant that exhibits increased tolerance to extreme acid pH proved sensitive to weak acids. Several insertions that rendered cells sensitive to organic acids were isolated, all of which proved to be linked to the rpoS locus.


A comparative study between myo-inositol and metformin in the treatment of insulin-resistant women.
Insulin resistance (IR) is a common disorder, which can impair female fertility and is characterized by phenotypic heterogeneity. Life-style treatment and insulin sensitizers are commonly used in the management of women with IR and consequent hyperinsulinemia, in order to restore the normal endocrinological and clinical parameters. Metformin (MET) is considered one of the first approaches to this pathology but new evidences are showing promising results using myo-inositol (MYO) in the management of this pathology. The aim of this retrospective data analysis was to evaluate the therapeutic efficacy of MYO (4 g myo-inositol plus 400 mcg folic acid/day) versus MET (on average 1225 mg/day) treatment in a heterogeneous group of IR patients. The focus was on progesterone and prolactin levels, menstrual cycle disorders, pregnancy rates, serum fasting glucose and insulin levels. Records about 6 months treatment (MYO or MET or both insulin sensitizers) at 237 women in reproductive age were analyzed retrospectively. The patients showed symptoms of IR without diabetes or pre diabetes. All the groups showed a significant improvement (p<0.05) in prolactin and progesterone level after the treatment. Furthermore, the treated groups reported a significant improvement in the menstrual cycle disorders, while the only life-style group showed an increase but not statistically significant (p>0.05). MYO and MET, associated with life-style, had both significant beneficial effects on serum progesterone and prolactin levels, menstrual cycle disorders and pregnancy rates in patients without severe carbohydrate metabolism malfunctions. Nevertheless, no significant differences were found between the MET and the MYO groups. Significant results in hormone levels and symptoms were reached with the combination of both treatments, whereas fasting serum insulin levels were slightly improved. Furthermore, the body mass index (BMI) was moderately but not significantly higher in MET and MET+MYO group.


Electromyographic evaluation of malignant hyperthermia-susceptible pigs.
Electromyography, with the aid of telemetry, was used to examine muscles of 4 young and 4 adult pigs from a genetic line highly susceptible to malignant hyperthermia (MH) and 4 young pigs (controls) from a line with no history of susceptibility to MH. In the young pigs, the intercostales, vastus lateralis, triceps brachii, biceps femoris, and gastrocnemius muscles were examined, whereas in the adult pigs only the latter 3 were examined. Spontaneous electrical activity, such as fibrillation potentials and abnormal insertion activity, was not observed in the electromyograms, indicating that neither denervation nor muscle membrane hyperirritability was associated with MH susceptibility in these pigs. Amplitude and duration of motor unit potentials (MUP) in the young MH-susceptible (MHS) pigs were significantly larger (P less than 0.01) and longer (P less than 0.05), respectively, than these values for MUP in the control pigs. These changes are opposite in direction to those expected in a myopathy. The mean values (+/- SD) for amplitude and duration for all muscles were 300 +/- 160 microV and 3.2 +/- 0.7 ms, respectively, in the control pigs and 555 +/- microV and 3.6 +/- 0.3 ms, respectively, in the young MHS pigs. Mean values for amplitude and duration of MUP for the adult MHS pigs were larger than were those for the young MHS pigs, but the differences were not significant (P greater than 0.05).


[Use of aldactone-saltucine in patients with heart failure].
Aldactone-saltucine was used in 52 patients with Stage IIB-III cardiac failure. The efficiency of the drug was evaluated by the dynamics of the clinical course, diuresis, body weight, blood and urine levels of electrolytes, and in some patients by the urine excretion of aldosterone. Aldactone-saltucine is a sufficiently effective diuretic agent that, without producing excessively fast diuresis, exerts after a course of therapy a beneficial effect, increasing mainly natriuresis, without concomitant hypokalemia. The diuretic effect of the drug ensued irrespectful of the initial level of urine aldosterone excretion. After a course of treatment urine aldosterone excretion tended to increase. Hyperaldosteronuria was noted in only 1/3 of the patients.


Interventions for the treatment of Paget's disease of the vulva.
This is an updated version of the original Cochrane Review published in Issue 10, 2013.Extramammary Paget's disease is a rare form of superficial skin cancer. The most common site of involvement is the vulva. It is seen mainly in postmenopausal white women. Paget's disease of the vulva often spreads in an occult fashion, with margins extending beyond the apparent edges of the lesion. There is a range of interventions from surgical to non-invasive techniques or treatments. The challenges of interventions are to remove or treat disease that may not be visible, without overtreatment and with minimisation of morbidity from radical surgery. There is little consensus regarding treatment. Surgery, by default, is the most common treatment, but it is challenging to excise the disease adequately, and recurrence is common, leading to repeated operations, and destruction of anatomy. Alternative treatments of photodynamic therapy, laser therapy, radiotherapy, topical treatments or even chemotherapy have been mooted, and it is important to evaluate the available evidence. It is essential to assess whether newer cell-specific treatments, such as photodynamic therapy and imiquimod, can reduce the need for radical surgery. To evaluate the benefits and harms of different treatment modalities for the management of Paget's disease of the vulva. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (via Ovid) and Embase (via Ovid) up to 8 May 2018. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of review articles. We searched for randomised controlled trials (RCTs) and well-designed non-randomised studies that compared different interventions in women with Paget's disease of the vulva, DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and, therefore, analysed no data. The search for the original version of the review identified 635 unique references. We found 31 references (which reported on 30 studies) in full text after inspection of titles and abstracts, but we excluded them all as they did not meet the inclusion criteria. However, we have included a comprehensive narrative account of studies where we identified an analysis of more than 10 women, as this forms the only evidence base in this rare disease. Surgery continues to be the mainstay of treatment in the current literature, with other treatments limited to case reports or treatment of inoperable or recurrent disease.This update between September 2013 and May 2018 identified 35 new studies. None of these met the inclusion criteria. There was only one prospective study of 5% imiquimod in recurrent Paget's disease of the vulva, which although of good quality only included eight women. Since the last version of the review was published there are many more cases in the literature reporting a clinical response to 5% imiquimod cream. There is one prospective study of eight women treated with 5% imiquimod for recurrent Paget's disease of the vulva, and one prospective trial of 20 women was due to be reported. This increasing evidence for the safety and efficacy of 5% imiquimod will be helpful for women and clinicians alike. Ideally, a multicentre RCT of reasonable size is needed, but ongoing publications of high-quality non-randomised prospective studies will enhance the current available literature.


Illuminating the Prevalence of Trypanosoma brucei s.l. in Glossina Using LAMP as a Tool for Xenomonitoring.
As the reality of eliminating human African trypanosomiasis (HAT) by 2020 draws closer, the need to detect and identify the remaining areas of transmission increases. Here, we have explored the feasibility of using commercially available LAMP kits, designed to detect the Trypanozoon group of trypanosomes, as a xenomonitoring tool to screen tsetse flies for trypanosomes to be used in future epidemiological surveys. The DNA extraction method was simplified and worked with the LAMP kits to detect a single positive fly when pooled with 19 negative flies, and the absolute lowest limit of detection that the kits were able to work at was the equivalent of 0.1 trypanosome per ml. The DNA from Trypanosoma brucei brucei could be detected six days after the fly had taken a blood meal containing dead trypanosomes, and when confronted with a range of non-target species, from both laboratory-reared flies and wild-caught flies, the kits showed no evidence of cross-reacting. We have shown that it is possible to use a simplified DNA extraction method in conjunction with the pooling of tsetse flies to decrease the time it would take to screen large numbers of flies for the presence of Trypanozoon trypanosomes. The use of commercially-available LAMP kits provides a reliable and highly sensitive tool for xenomonitoring and identifying potential sleeping sickness transmission sites.


Feasibility of portable sleep monitors to detect obstructive sleep apnea (OSA) in a vulnerable urban population.
Portable sleep monitors may offer a convenient method to expand detection of obstructive sleep apnea (OSA), yet few studies have evaluated this technology in vulnerable populations. We therefore aimed to assess the feasibility and acceptability of portable sleep monitors for detection of OSA in a prediabetic, urban minority population. We recruited a convenience sample of participants at their 12-month follow-up for a community-partnered, peer-led lifestyle intervention aimed to prevent diabetes in prediabetic and overweight patients in this prospective mixed-methods pilot study. All participants wore portable sleep monitors overnight at home. We qualitatively explored perceptions about OSA and portable monitors in a subset of participants. We tested 72 people, predominantly non-White, female, Spanish speaking, uninsured, and of low income. Use of portable sleep monitors was feasible: 100% of the monitors were returned and all participants received results. We detected OSA in 49% (defined as an Apnea-Hypopnea Index [AHI] >5) and moderate-severe OSA in 14% (AHI >15) requiring treatment in 14%. In 21 qualitative interviews, participants supported increased use of portable sleep monitors in their community, were appropriately concerned that OSA could cause progression to diabetes, and thought weight loss could prevent or improve OSA. Portable sleep monitors may represent a feasible method for detecting OSA in high-risk urban minority populations.


Nonsaturation of AMPA and NMDA receptors at hippocampal synapses.
An important issue in synaptic physiology is the extent to which postsynaptic receptors are saturated by the neurotransmitter released from a single synaptic vesicle. Although the bulk of evidence supports receptor saturation, recent studies have started to reveal that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors may not be saturated by a single vesicle of glutamate. Here, we address this question through a study of putative single synapses, made by hippocampal neurons in culture, that are identified by FM1-43 staining. An analysis of the sources of variability in the amplitudes of miniature excitatory postsynaptic currents at single synapses reveals that this variability must arise presynaptically, from variations in the quantity of agonist released. Thus, glutamate receptors at hippocampal synapses are not generally saturated by quantal release.


The first fungi: mode of delivery determines early life fungal colonization in the intestine of preterm infants.
Aim: The role of intestinal fungi in human health and disease is becoming more evident. The mycobiota composition and diversity of preterm infants is affected by interactions with bacteria and clinical variables. In this study, we aimed to characterize the composition and the diversity of the preterm infant mycobiota and the effect of clinical variables on it in the first six postnatal weeks. Methods: Preterm infants (n = 50) and full-term infants (n = 6) admitted to Isala Women and Children's hospital (Zwolle, The Netherlands) who were born during 24-36 or 37-40 weeks of gestation, respectively, were included in this study. Feces were collected during the first six postnatal weeks (n = 109) and their mycobiota composition and diversity were characterized by ITS2 amplicon sequencing. Results: Composition analyses identified fungi and other eukaryotic kingdoms, of which Viridiplantae was most abundant. Of the fungal kingdom, Ascomycota and Basidiomycota were the first and second most prominent phyla in early life of all infants. Candida was the most abundant genus in the first six weeks of life and increased with gestational and postnatal age. Fungal phylogenetic diversity remained stable in the first six postnatal weeks. The individuality and the mode of delivery were identified as significant predictors for the variation in the mycobiota composition. Vaginally delivered infants were enriched in Candida spp., whereas infants delivered through emergency C-section were characterized by Malassezia spp. Conclusion: These results indicate that fungi and other eukaryotic kingdoms are detected in the intestine of preterm and full-term infants in the first six postnatal weeks. Similar to the microbiota, colonization of the preterm intestine with fungi is determined by clinical variables including individuality and mode of delivery.


Intra-venous albumin for preventing severe ovarian hyperstimulation syndrome.
Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic condition that occurs after the administration of human menopausal gonadotrophin (hMG) with or without gonadotrophin releasing hormone (GnRH) agonists. OHSS is a threat to every woman undergoing ovulation induction and is potentially lethal in its severest form. Severe OHSS is characterised by growth of multiple large follicles with massive extravascular protein rich fluid shift. This may lead to hypovolaemia, haemoconcentration, oliguria, and electrolyte disturbance. Human albumin solutions are now used in the management of shock and other conditions in which restoration of blood volume is urgent, the acute management of burns, and clinical situations associated with hypoproteinaemia. Recently, a number of clinical trials with conflicting results have been reported in which albumin has been tested as a possible way for preventing the severe form of OHSS. To review the effectiveness of human albumin administration in prevention of severe ovarian hyperstimulation syndrome. The Menstrual Disorders and Subfertility Group literature search strategy was used to identify randomised trials that had compared the use of human albumin with placebo or no treatment in the prevention of severe ovarian hyperstimulation syndrome. A diverse search strategy was employed, including handsearching of core journals from 1966 to the present, searching bibliographies of relevant trials, MEDLINE, EMBASE, PsychLIT and CINAHL databases, the MDSG specialised register, abstracts from North American and European meetings and contact with authors of relevant papers. Trials were included if they compared the effect of human albumin with placebo or no treatment on relevant outcomes. Only randomised controlled studies were included in this review. Trials under consideration were evaluated for methodological quality and appropriateness for inclusion without consideration of their results. Relevant data were extracted independently by two reviewers using the standardized data extraction sheet. Validity was assessed in terms of method of randomization, completeness of follow-up, presence or absence of crossover and co-intervention. 2x2 tables were generated for all relevant outcomes. Odds ratios were calculated using the Peto modified Mantel-Haenszel technique. Meta-analysis of the three included trials demonstrated significant reduction in severe ovarian hyperstimulation syndrome on administration of human albumin (common odds ratio 0.1, 95% confidence interval 0.03 to 0.39). There was no evidence of an increase in the pregnancy rate (common odds ratio 1.69, 95% confidence interval 0.7 to 4.07). This review shows a clear benefit from administration of intra-venous albumin at the time of oocyte retrieval in prevention of severe OHSS in high-risk cases. However, the results of this review can not be regarded as conclusive as they are based on only three small trials. Further trials are urgently needed.


Inositol hexaphosphate (InsP6) as an effective topical treatment for patients receiving adjuvant chemotherapy after breast surgery.
Oral treatment with inositol hexaphosphate (InsP6) has shown to be efficient in decreasing adverse effects in patients with breast cancer under chemotherapy. This study was aimed at evaluating and comparing the efficacy of topical InsP6 in improving quality of life in women treated with anticancer drugs. The study was a double-blind, randomized controlled trial (RCT) with allocation concealment of 20 patients in two groups, one (experimental) applied 4% topical formulation of InsP6 once a day, whereas the second one (control) a gel containing hyaluronic acid. InsP6 therapy started 6 weeks after lumpectomy. Blood tests were monitored in both groups and quality of life was assessed using standardized QLQ-C30 and QLQ-BR23. Patients who applied InsP6 on the breast significantly improved their quality of life and functional status reducing side effects compared to control group; moreover, after treatment, a significant difference between the two groups was observed in the white blood cells and platelets count values. Topical InsP6 treatment has demonstrated to be effective and safe in preventing and/or mitigating chemotherapy-induced side effects as well as the preserving quality of life in women with ductal breast cancer.


Age-related declines in exploratory behavior and markers of hippocampal plasticity are attenuated by prenatal choline supplementation in rats.
Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline-supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12-17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal choline supplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age.


Outcome analysis of reduction mammaplasty using the modified Robertson technique.
The benefits of reduction mammaplasty have been well documented in previous literature. Anticipating and correcting for pseudoptosis (bottoming-out), however, can impair the cosmetic outcome as the inferior skin envelope stretches and lengthens over time. We present long-term results on patients using the modified Robertson technique for reduction mammaplasty, which appears to have significant benefit in helping to prevent bottoming-out. Surveys were sent to patients undergoing reduction mammaplasty surgery with this technique from 1987 to 1997. Patients were queried regarding preoperative and postoperative symptoms, satisfaction, and outcome related to their surgery and were also offered free follow-up examinations. The patients who returned for follow-up were then evaluated by the attending surgeons for evaluation of scarring, nipple position, ptosis, pseudoptosis, shape, and overall appearance. Reduced breasts were also compared with cosmetically optimal breasts to compare for measured levels of pseudoptosis using our defined visual inferior pole ratio measurements. Average reduction size was 910 g and follow-up was 4.7 years from the time of surgery. There was significant improvement demonstrated in all areas questioned, with the greatest relief shown in back and shoulder pain, shoulder grooving, and difficulty fitting clothing. There was also demonstrated to be significantly less use of medical modalities postoperatively and significant increases in activity levels. Satisfaction for size, shape, symmetry, and overall results was 85, 94, 98, and 94 percent, respectively. Evaluations for pseudoptosis by the attending surgeons were rated good or excellent in 95 percent of patients. Measurements of the visual inferior pole ratio for pseudoptosis also demonstrated no significant differences when compared with aesthetically optimal breasts. The modified Robertson reduction mammaplasty is a reliable technique that can be used for both small and large reductions, giving both reliable and consistent results. This technique significantly improves symptoms, as do other reduction techniques, but has the added advantage of helping to avoid pseudoptosis postoperatively.


Long-term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer.
The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and there are only a few standard treatments. We conducted a phase I trial to investigate the safety, immune response, and antitumor effect of vaccination with four peptides derived from cancer-testis antigens, with a focus on their fluctuations during long-term vaccination until the disease had progressed. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. HLA-A*2402-restricted epitope peptides, lymphocyte antigen 6 complex locus K, TTK protein kinase, insulin-like growth factor-II mRNA-binding protein 3, and DEP domain containing 1 were vaccinated subcutaneously once a week at doses of 0.5, 1, or 2 mg and continued until disease progression. The adverse events were assessed by Common Terminology Criteria for Adverse Events and the immune response was monitored by an enzyme-linked immunospot assay or by flow cytometry. The clinical effects observed were tumor response, progression-free survival (PFS), and overall survival (OS). Four-peptide vaccination was well tolerated. No grade 3 or 4 adverse events were observed. Peptide-specific T-cell immune responses were observed in seven of nine patients and clinical responses were observed in six of nine patients. The median PFS and OS were 156 and 380 days. The injection site reaction and CTL induction seemed to be prognostic factors of both PFS and OS. Four-peptide vaccination was well tolerated and seemed to provide some clinical benefit to some patients. These immunologic and clinical responses were maintained over the long term through continuous vaccinations.


Activation of nonclassical CD1d-restricted NK T cells induces airway hyperreactivity in beta 2-microglobulin-deficient mice.
Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in beta(2)-microglobulin (beta(2)m)(-/-) mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1(+) noninvariant TCR NKT cell population is present in beta(2)m(-/-) mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of beta(2)m(-/-) mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to alpha-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a beta(2)m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR.


Short- vs long-duration antibiotic regimens for ventilator-associated pneumonia: a systematic review and meta-analysis.
We performed a systematic review and meta-analysis of short- vs long-duration antibiotic regimens for ventilator-associated pneumonia (VAP). We searched PubMed and Cochrane Central Registry of Controlled Trials. Four randomized controlled trials (RCTs) comparing short (7-8 days) with long (10-15 days) regimens were identified. Primary outcomes included mortality, antibiotic-free days, and clinical and microbiologic relapses. Secondary outcomes included mechanical ventilation-free days, duration of mechanical ventilation, and length of ICU stay. All RCTs included mortality data, whereas data on relapse and antibiotic-free days were provided in three and two out of four RCTs, respectively. No difference in mortality was found between the compared arms (fixed effect model [FEM]: OR = 1.20; 95% CI, 0.84-1.72; P = .32). There was an increase in antibiotic-free days in favor of the short-course treatment with a pooled weighted mean difference of 3.40 days (random effects model: 95% CI, 1.43-5.37; P < .001). There was no difference in relapses between the compared arms, although a strong trend to lower relapses in the long-course treatment was observed (FEM: OR = 1.67; 95% CI, 0.99-2.83; P = .06). No difference was found between the two arms regarding the remaining outcomes. Sensitivity analyses yielded similar results. Short-course treatment of VAP was associated with more antibiotic-free days. No difference was found regarding mortality and relapses; however, a strong trend for fewer relapses was observed in favor of the long-course treatment, being mostly driven by one study in which the observed relapses were probably more microbiologic than clinical. Additional research is required to elucidate the issue.


Selective recording of neuroelectric activity from the peripheral nerve.
Electroneurograms (ENGs) from superficial regions of the sciatic nerve of a dog, innervating the tibialis anterior (TA) and gastrocnemius muscles (GM), arising mainly from muscle spindles and Golgi tendon organs were recorded selectively with an implanted 33-electrode spiral cuff (cuff). Relative positions of superficial regions within the cuff were defined by delivering stimulating pulses on groups of three electrodes (GTEs) within the cuff which were in contact with them. It was found that GTEs eliciting maximum contractions of muscles were GTE No. 3 for the TA muscle and GTE No. 8 for the GM muscle. In the first experiment the implanted leg was mounted into a special electronic brace. Extending forces were applied to the ankle rotating it by up to +/-37 degrees according to the neutral position, thus eliciting torques in the TA muscle of up to 1.2 Nm. Channel 1 of the 4-channel preamplifier was connected to GTE No. 8, channel 2 to GTE No. 2, channel 3 to GTE No. 11 and channel 4 to GTE No. 5. Results show that only ENG recorded with GTE No. 8, being close to the region innervating the TA muscle, correspond to the mechanical load. In the second experiment the calcanean tendon (CT) of an implanted leg was dissected. The proximal end of the CT was connected to a force transducer and repetitive pull forces (about 12 N) were applied to the CT. Channel 1 of the preamplifier was connected to GTE No. 5, channel 2 to GTE No. 1, channel 3 to the GTE No. 11 and channel 4 to GTE No. 8. Results show that only ENG recorded with GTE No. 5, being close to the region innervating the GM muscle, correspond to the mechanical load applied on CT.


Epidemiologic features of Strongyloides stercoralis infection in an endemic area of the United States.
The epidemiologic features of Strongyloides stercoralis infection in Kentucky were studied by an analysis of clinical cases at the University of Kentucky Medical Center (UKMC); by an analysis of parasitologic records of the Kentucky Bureau for Health Services (KBHS); and by a prospective stool survey of school children in Clay County, located in southeastern Kentucky, an area of the state previously found to be highly endemic for intestinal parasites. S. stercoralis was the most common parasitic infection diagnosed at UKMC. The patients were predominantly white male adults who were over 50 years old, had an associated chronic or debilitating medical illness, were of low socioeconomic background, and resided in southeastern Kentucky. S. stercoralis was a common parasitic infection at KBHS ad the patients showed a similar geographic distribution. Of 561 Clay County children surveyed, 23.7% harbored one or more intestinal parasite pathogens and 3.0% had S. stercoralis. Thus, S. stercoralis remains highly endemic in Kentucky and may cause disease even in geriatric patients.


Monitoring fast chemical processes by reaction-interrupted excitation transfer (ExTra) NMR spectroscopy.
NMR spectroscopy is generally used to investigate molecules under equilibrium conditions. Despite recent technological and methodogical developments to study on-going reactions, tracing the fate of individual atoms during an irreversible chemical reaction is still a challenging and elaborate task. Reaction-interrupted excitation transfer (ExTra) NMR provides a selective tracking of resonances from atoms, which undergo chemical conversion. We show that reactions triggered either by rapid mixing or by photo-excitation can be conveniently followed at a sub-second time scale using standard NMR equipment. In ExTra NMR we use the selectively inverted magnetization of a selected atom to follow its conversion in the course of a fast chemical reaction. The chemical reaction has to be started within the relaxation period of an initial inverting 180° pulse. The presented protocol provides a generally applicable NMR method for reaction monitoring.


Multiple sclerosis: molecular mechanisms and therapeutic opportunities.
The pathophysiology of multiple sclerosis (MS) involves several components: redox, inflammatory/autoimmune, vascular, and neurodegenerative. All of them are supported by the intertwined lines of evidence, and none of them should be written off. However, the exact mechanisms of MS initiation, its development, and progression are still elusive, despite the impressive pace by which the data on MS are accumulating. In this review, we will try to integrate the current facts and concepts, focusing on the role of redox changes and various reactive species in MS. Knowing the schedule of initial changes in pathogenic factors and the key turning points, as well as understanding the redox processes involved in MS pathogenesis is the way to enable MS prevention, early treatment, and the development of therapies that target specific pathophysiological components of the heterogeneous mechanisms of MS, which could alleviate the symptoms and hopefully stop MS. Pertinent to this, we will outline (i) redox processes involved in MS initiation; (ii) the role of reactive species in inflammation; (iii) prooxidative changes responsible for neurodegeneration; and (iv) the potential of antioxidative therapy.


Emotional and experiential factors that determine civilizational diseases.
The effects of adverse childhood experiences may persist in adult life and manifest themselves in various areas of functioning. The aim of the study was to identify the emotional and experiential factors that determine civilizational diseases and the methods of regulating emotions and functioning in society. The surveyed group was composed of 141 adults. The respondents defined the existence of adverse experiences and their attachment styles in retrospective. The methods of regulating emotions were also measured, as well as the presence of civilizational diseases. The authors found a correlation between the style of attachment and the traumatic events experienced during the first 18 years of life and the existence of civilizational diseases. Adverse experiences in childhood and attachment styles proved to be predictors of specific social behaviour aimed at regulating emotions. The results emphasised the importance of the bond with a parent and of traumatic childhood experiences for the future health condition and for the social and emotional functioning. The study demonstrated that persons who experienced traumatic events in their families or in the peer environment in the first 18 years of their lives reported the presence of civilizational diseases. A correlation was found between peer violence, the threat of being abandoned by a caregiver, and diagnosed civilizational diseases in respondents. The fearful-ambivalent style in the relationship with the father proved to be a predictor of reported civilizational diseases. Adverse childhood experiences are linked to regulating emotions by taking perspective. The attachment style developed in the relationship with parents determined the ways of regulating negative and positive emotions in contact with other people. Persons who developed an avoidant attachment style in the relationships with the mother or the father less frequently seek social support when they experience negative emotions.


Ubiquitin-specific protease16 modulates salt tolerance in Arabidopsis by regulating Na(+)/H(+) antiport activity and serine hydroxymethyltransferase stability.
Protein ubiquitination is a reversible process catalyzed by ubiquitin ligases and ubiquitin-specific proteases (UBPs). We report the identification and characterization of UBP16 in Arabidopsis thaliana. UBP16 is a functional ubiquitin-specific protease and its enzyme activity is required for salt tolerance. Plants lacking UBP16 were hypersensitive to salt stress and accumulated more sodium and less potassium. UBP16 positively regulated plasma membrane Na(+)/H(+) antiport activity. Through yeast two-hybrid screening, we identified a putative target of UBP16, SERINE HYDROXYMETHYLTRANSFERASE1 (SHM1), which has previously been reported to be involved in photorespiration and salt tolerance in Arabidopsis. We found that SHM1 is degraded in a 26S proteasome-dependent process, and UBP16 stabilizes SHM1 by removing the conjugated ubiquitin. Ser hydroxymethyltransferase activity is lower in the ubp16 mutant than in the wild type but higher than in the shm1 mutant. During salt stress, UBP16 and SHM1 function in preventing cell death and reducing reactive oxygen species accumulation, activities that are correlated with increasing Na(+)/H(+) antiport activity. Overexpression of SHM1 in the ubp16 mutant partially rescues its salt-sensitive phenotype. Taken together, our results suggest that UBP16 is involved in salt tolerance in Arabidopsis by modulating sodium transport activity and repressing cell death at least partially through modulating SMH1stability and activity.


A Combinatorial Optimization Framework for Scoring Students in University Admissions.
Selecting applications for college admission is critical for university operation and development. This paper leverages machine learning techniques to support enrollment management teams through data-informed decision-making in this otherwise laborious admissions processing. Two aspects of university admissions are considered. An ensemble learning approach, through the SuperLearner algorithm, is used to predict student show (yield) rate. The goal is to improve prediction accuracy to minimize over- or under-enrollment. A combinatorial optimization framework is proposed to weigh academic performance and experiential factors for ranking and selecting students for admission. This framework uses simulated annealing, and an efficacy study is presented to evaluate performance. The proposed framework is illustrated for selecting an incoming class by optimizing predicted graduation rate and by developing an eligibility index. Each example presents a selection process under potential academic performance and experiential factor targets a university may place on an admitted class. R code is provided for higher education researchers and practitioners to apply the proposed methods in their own settings.


Enhanced peptide beta-sheet affinity by metal to ligand coordination.
A histidine-coordinating metal complex substituted with methoxypyrrole amino acids (MOPAS) as a peptide beta-sheet binder shows high affinity for a H(2)N-His-Leu-Leu-Val-Phe-OMe pentapeptide in DMSO solution. Within the complex, a beta-sheet conformation is induced into the pentapeptide by weak intra-assembly interactions with the MOPAS units.


Preparation and characterization of novel polytitanium tetrachloride coagulant for water purification.
Polymeric metal coagulants are increasingly being used to improve coagulation efficiency, yet the research on the development of titanium and particularly polytitanium salts remains limited. This study is the first attempt in the synthesis, characterization, and application of polytitanium salts as coagulants. Polytitanium tetrachloride (PTC) solutions with different basicity values B (OH/Ti molar ratio) were prepared using a slow alkaline titration method. Jar tests were conducted to assess coagulation performance using both synthetic and real raw water samples, and the floc characteristics were monitored online using a laser diffraction particle size analyzer. Electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) was utilized to identify various Ti species, with the results providing strong evidence of the presence of various hydrolyzed Ti species in the titanium aqueous phase. Compared to titanium tetrachloride (TiCl4), higher or comparable turbidity and organic matter removal efficiency could be achieved by PTC with improved floc characteristics in terms of size, growth rate, and structure. Besides, the water pH after PTC coagulation was significantly improved toward neutral pH. This study indicates that PTC is an effective and promising coagulant for water purification. Besides, the PTC flocculated sludge was able to recycle and produce functional TiO2 photocatalyst.


The spontaneous bacterial peritonitis in cirrhotic patients. To a new gold standard.
Of 282 consecutive ascites prospectively collected in 54 months, Spontaneous Bacterial Peritonitis (SBP) was diagnosed in 8.5% of the cases, "probable" SBP in 31.1%, Bacteriascites (BA) in 3.5% and Sterile Ascites (SA) (negative ascitic fluid culture with PMN less than 250/mm3) in 74.8%. Escherichia Coli (41.6%) and Staphylococcus Epidermidis (60%) were the most frequent pathogens isolated in patients with SBP and BA, respectively. With regards to in-hospital mortality, 18% of patients with BA and 50% with SBP died; the mortality seemed to be related to the degree of hepatic and renal damage, to a higher peripheral and ascitic WBC concentration and to a lower pH of ascitic fluid (FA). When the comparative analysis was applied to the four groups of ascites, a different distribution of clinical signs and biohumoral parameters appeared. As a matter of fact, abdominal pain, fever and rebound tenderness resulted significantly more frequent in SBP and "probable" SBP. Furthermore, the mean values of peripheral and ascitic WBC concentration, of serum creatinine and of ALT were statistically higher in SBP and "probable" SBP than in SA and BA groups. The strict relationship, both symptomatologic and biochemical, between SA and BA on the one hand and between "probable" SBP and SBP on the other, prompted us to conclude that "probable" SBP and SBP represent different patterns of the same disease. Therefore, the subclassification in the four groups outlined above would not be in accordance with the clinical practice and could give rise to the physician's confusion and uncertainty.


β-Blocker use and reduced disease progression in patients with thick melanoma: 8 years of follow-up.
Previous observational studies have reported the protective effect of β-blockers on the progression of different types of cancers. In 2011, we published a prospective study, including patients with histologically confirmed malignant melanoma in stage II-IIIA. In total, 25% of them reported previous use of β-blockers that were administered at any time for any other diseases. After a median follow-up of 2.5 years, 34% of the patients in the untreated group showed disease progression. In contrast, only 3% of the patients in the treated group showed progression. We report the findings obtained in the same cohort after a longer period of β-blocker therapy and follow-up (8 years). We prospectively reviewed data of the patients enrolled in the original prospective study. Disease progression was assessed by evaluating the presence of lymphatic, in-transit or visceral metastases. Deaths by any cause and deaths because of melanoma were recorded. A multivariate Cox proportional hazards model was used to evaluate the effect of β-blocker use on disease-free survival and overall survival, adjusting for significant confounders. After a median follow-up of 8 years and a median duration of β-blocker use of 7.6 years, 45% of the patients in the untreated group and 30% of the patients in the treated group showed disease progression. Notably, in the untreated group 35% patients died from melanoma and only 17% patients died from melanoma in the treated group. Results of this hospital-based prospective cohort study with a median follow-up of 8 years confirmed our previous results that the use of β-blockers significantly reduced the risk of recurrence and mortality in melanoma patients.


Functional expression of aryl-alcohol oxidase in Saccharomyces cerevisiae and Pichia pastoris by directed evolution.
Aryl-alcohol oxidase (AAO) plays a fundamental role in the fungal ligninolytic secretome, acting as a supplier of H2 O2 . Despite its highly selective mechanism of action, the presence of this flavooxidase in different biotechnological settings has hitherto been hampered by the lack of appropriate heterologous expression systems. We recently described the functional expression of the AAO from Pleurotus eryngii in Saccharomyces cerevisiae by fusing a chimeric signal peptide (preαproK) and applying structure-guided evolution. Here, we have obtained an AAO secretion variant that is readily expressed in S. cerevisiae and overproduced in Pichia pastoris. First, the functional expression of AAO in S. cerevisiae was enhanced through the in vivo shuffling of a panel of secretion variants, followed by the focused evolution of the preαproK peptide. The outcome of this evolutionary campaign-an expression variant that accumulated 4 mutations in the chimeric signal peptide, plus two mutations in the mature protein- showed 350-fold improved secretion (4.5 mg/L) and was stable. This secretion mutant was cloned into P. pastoris and fermented in a fed-batch bioreactor to enhance production to 25 mg/L. While both recombinant AAO from S. cerevisiae and P. pastoris were subjected to the same N-terminal processing and had a similar pH activity profile, they differed in their kinetic parameters and thermostability. The strong glycosylation observed in the evolved AAO from S. cerevisiae underpinned this effect, since when the mutant was produced in the glycosylation-deficient S. cerevisiae strain Δkre2, its kinetic parameters and thermostability were comparable to its poorly glycosylated P. pastoris recombinant counterpart.


Persistent nasal carriage of Staphylococcus aureus is associated with deficient induction of human beta-defensin 3 after sterile wounding of healthy skin in vivo.
Persistent nasal carriage of Staphylococcus aureus is the primary reservoir for this pathogen and a risk factor for infection. The nares of 12 to 30% of healthy individuals are persistently colonized with staphylococci. Elucidating the yet enigmatic determinants of this phenomenon is of major public health interest. We hypothesized that differences in the levels of antimicrobial peptides (AMPs) that are found in human skin and have pronounced antistaphylococcal activity may contribute to this phenomenon. We compared constitutive and induced mRNA levels of RNase 7 and human β-defensin 3 (HBD-3) in healthy and experimentally wounded gluteal skin of 60 volunteers after ascertaining their carrier status through repeated nasal cultures. We found that levels of HBD-3 expression in skin of persistent nasal carriers of S. aureus were lower: induced levels in carriers were 63% (95% confidence interval, 43 to 94%; P = 0.02) and constitutive levels were 76% (95% confidence interval, 52 to 110%; P = 0.14) of those found in noncarriers. No such associations were present for RNase 7. In conjunction with existing knowledge, these findings suggest that healthy individuals with deficient HBD-3 expression in keratinocytes are more prone to persistent nasal colonization with S. aureus.


Effectiveness of Serious Games for Leap Motion on the Functionality of the Upper Limb in Parkinson's Disease: A Feasibility Study.
The design and application of Serious Games (SG) based on the Leap Motion sensor are presented as a tool to support the rehabilitation therapies for upper limbs. Initially, the design principles and their implementation are described, focusing on improving both unilateral and bilateral manual dexterity and coordination. The design of the games has been supervised by specialized therapists. To assess the therapeutic effectiveness of the proposed system, a protocol of trials with Parkinson's patients has been defined. Evaluations of the physical condition of the participants in the study, at the beginning and at the end of the treatment, are carried out using standard tests. The specific measurements of each game give the therapist more detailed information about the patients' evolution after finishing the planned protocol. The obtained results support the fact that the set of developed video games can be combined to define different therapy protocols and that the information obtained is richer than the one obtained through current clinical metrics, serving as method of motor function assessment.