[Impact of premature birth on long term cardio-cerebral vascular events of puerpera].
To investigate the impact of premature birth on long term cardio-cerebral vascular events of puerpera. Ambispective cohort study method was used and 3 659 pregnant women giving birth during October 1976 to December 2008 at Kailuan medical group were included and divided into premature birth (PTB) group (n = 226) and non-PTB (NPTB) group (n = 3 433) by the history of PTB. Incidence of cardio-cerebral vascular events (myocardial infarction, cerebral infarction and cerebral hemorrhage) was obtained during follow-up. Multivariable Cox proportional hazards regression models was used to assess the relative risk of cardio-cerebral vascular events. (1) The childbearing age, proportion of pregnancy-induced hypertension, systolic blood pressure and diastolic blood pressure before delivery were significantly higher while weight and height of newborn were significantly less in PTB group than in NPTB group (P < 0.05 or 0.01). (2) There were 71 cardio-cerebral vascular events during the follow-up of (15.19 ± 7.75) years. In PTB group, the incidence of cardio-cerebral vascular events and myocardial infarction was 3.23/1 000 person-years and 2.05/1 000 person-years, respectively, while the corresponding incidence was 1.15/1 000 person-years and 0.42/1 000 person-years, respectively in NPTB group (all P < 0.05). After adjustment for other traditional cardiovascular risk factors, the risk of total cardio-cerebral vascular events, myocardial infarction in PTB group was 2.03 fold (95% CI: 1.02-4.04, P = 0.002) and 3.11 fold (95% CI: 1.18-8.18, P < 0.001) higher than in NPTB group. PTB is an independent risk factor for total cardio-cerebral vascular events, especially myocardial infarction of puerpera.


Hydrophobic Amines and Their Guanidine Analogues Modulate Activation and Desensitization of ASIC3.
Acid-sensing ion channel 3 (ASIC3) is an important member of the acid-sensing ion channels family, which is widely expressed in the peripheral nervous system and contributes to pain sensation. ASICs are targeted by various drugs and toxins. However, mechanisms and structural determinants of ligands' action on ASIC3 are not completely understood. In the present work we studied ASIC3 modulation by a series of "hydrophobic monoamines" and their guanidine analogs, which were previously characterized to affect other ASIC channels via multiple mechanisms. Electrophysiological analysis of action via whole-cell patch clamp method was performed using rat ASIC3 expressed in Chinese hamster ovary (CHO) cells. We found that the compounds studied inhibited ASIC3 activation by inducing acidic shift of proton sensitivity and slowed channel desensitization, which was accompanied by a decrease of the equilibrium desensitization level. The total effect of the drugs on the sustained ASIC3-mediated currents was the sum of these opposite effects. It is demonstrated that drugs' action on activation and desensitization differed in their structural requirements, kinetics of action, and concentration and state dependencies. Taken together, these findings suggest that effects on activation and desensitization are independent and are likely mediated by drugs binding to distinct sites in ASIC3.


An indoleacetate-CoA ligase and a phenylsuccinyl-CoA transferase involved in anaerobic metabolism of auxin.
The plant hormone auxin (indoleacetate) is anaerobically degraded by the Betaproteobacterium Aromatoleum aromaticum. We report here on a CoA ligase (IaaB) and a CoA-transferase (IaaL) which are encoded in the apparent substrate-induced iaa operon containing genes for indoleacetate degradation. IaaB is a highly specific indoleacetate-CoA ligase which activates indoleacetate to the CoA-thioester immediately after uptake into the cytoplasm. This enzyme only activates indoleacetate and some closely related compounds such as naphthylacetate, phenylacetate and indolepropionate, and is inhibited by high concentrations of substrates, and by the synthetic auxin compound 2,4-dichlorophenoxyacetate, which does not serve as substrate. IaaL is a CoA-transferase recognizing several C4-dicarboxylic acids, such as succinate, phenylsuccinate or benzylsuccinate and their CoA-thioesters, but only few monocarboxylic acids and no C3-dicarboxylic acids such as benzylmalonate. The enzyme shows no stereospecific discrimation of the benzylsuccinate enantiomers. Moreover, benzylsuccinate is regiospecifically activated to 2-benzylsuccinyl-CoA, whereas phenylsuccinate is converted to an equal mixture of both regioisomers (2- and 3-phenylsuccinyl-CoA). The identification of these two enzymes allows us to set up a modified version of the metabolic pathway of anaerobic indoleacetate degradation and to investigate the sequences databases for the occurrence and distribution of this pathway in other microorgansisms.


Utility of Precision Oncology Using Cancer Genomic Profiling for Head and Neck Malignancies.
In recent years, individual patient cancer genomic profiling (CGP) has become more accessible, allowing determination of therapeutic strategies using driver gene mutations in cancer therapy. However, this precision oncology approach, tailored to specific patients, remains experimental. In this study, we verified the feasibility and benefit of using CGP to guide treatment of malignant head and neck tumors. We aimed to evaluate the profiling and clinical courses of patients with head and neck malignancies who underwent CGP and determine the extent to which CGP for head and neck malignancies has resulted in beneficial drug administration. We analyzed CGP results, prognosis, and drug administration status in 27 patients. These patients had completed (or were expected to complete) standard therapy or had rare cancers without standard therapy. At least one somatic actionable gene alteration was seen in 25 (92.6%) patients, with a median number of actionable alterations per patient of 4 (range=0-11). Drugs in clinical trials were recommended to 22 (81.5%) patients, but none could participate. However, 3 patients (11.1%) could use approved drugs off-label based on CGP results. The most common genetic abnormality was TP53 (66.7%), with TP53 mutations leading to poor prognosis. CGP is clinically useful and serves as a bridge to increase the number of therapeutic options. However, candidate drugs confirmed using CGP may be ineffective when administered. Therefore, oncologists should not blindly accept CGP therapeutic recommendations but should make recommendations that lead to optimal therapies after proper verification.


Caudal septal deviation correction by interlocked graft technique.
In this prospective study, we have proposed a new method to straighten the caudal septum using a modified spreader graft interlocked on the convex side. A single-interlocked graft inserted by 2 through-and-through serial sections of the quadrangular cartilage (applied over the misshapen convex side previously scored on the concave side) facilitated adjustment of the distal septum intraoperatively. The strip of cartilage of the desired height and width acted as a spring graft and may be placed at the desired height of the caudal septal area to exactly counteract the eventual tendency of the most deviated area to warp over time. All 15 patients treated had improvement of their nasal airway and in their postoperative appearance of the external and internal nose. Our technique is easy to perform and shows long-term reliability in correcting caudal septal deviation, demanding a wider application to confirm its effectiveness on a larger series of patients.


The Effect of Dietary Interventions on Hypertriglyceridemia: From Public Health to Molecular Nutrition Evidence.
Approximately 25-50% of the population worldwide exhibits serum triglycerides (TG) (≥150 mg/dL) which are associated with an increased level of highly atherogenic remnant-like particles, non-alcoholic fatty liver disease, and pancreatitis risk. High serum TG levels could be related to cardiovascular disease, which is the most prevalent cause of mortality in Western countries. The etiology of hypertriglyceridemia (HTG) is multifactorial and can be classified as primary and secondary causes. Among the primary causes are genetic disorders. On the other hand, secondary causes of HTG comprise lifestyle factors, medical conditions, and drugs. Among lifestyle changes, adequate diets and nutrition are the initial steps to treat and prevent serum lipid alterations. Dietary intervention for HTG is recommended in order to modify the amount of macronutrients. Macronutrient distribution changes such as fat or protein, low-carbohydrate diets, and caloric restriction seem to be effective strategies in reducing TG levels. Particularly, the Mediterranean diet is the dietary pattern with the most consistent evidence for efficacy in HTG while the use of omega-3 supplements consumption is the dietary component with the highest number of randomized clinical trials (RCT) carried out with effective results on reducing TG. The aim of this review was to provide a better comprehension between human nutrition and lipid metabolism.


Osmolar changes regulate the paracellular permeability of cultured human cervical epithelium.
Extracellular nucleotides induce a biphasic change in the transepithelial electrical conductance (GT) of human cervical cells grown on filters: a rapid increase (phase I) followed by a sustained decrease (phase II). To probe the involvement of the intercellular space, its magnitude was varied by manipulating cell volume through changes in extracellular osmolarity. Under baseline conditions [GT = 115 mS/cm2 (approximately 9 omega.cm2)] and during phase II, hypertonic challenges resulted in an increase in GT (0.98% .mosmol-1.l-1 and 0.73%.mosmol-1.l-1, respectively). However, a hypertonic challenge during phase I decreased GT (-0.16%.mosmol-1.l-1). Hypotonic challenges decreased GT during baseline, phase I, and phase II conditions by -1%.mosmol-1.l-1. Similar trends were observed with regard to pyranine permeability. Reduction of extracellular calcium increased GT, abrogated the phase II effect of extracellular ATP, and reversed the effect of a hypertonic challenge. The additive nature of the permeability changes in response to osmotic challenges and to ATP during phase II suggests that different sites are involved in each response, i.e., the resistance of the intercellular space changes with osmolarity and that of the tight junction during phase II.


Biology of HPV in HIV infection.
HIV-positive men and women are at increased risk of anogenital and oral HPV infection. The risks for HPV-associated high-grade intra-epithelial neoplasia (IN) and cancer are also increased. The prevalence of oral, anal, and cervical HPV infection in HIV-positive individuals compared with HIV-negative individuals increases with progressively lower CD4+ levels, as does incident high-grade IN. In contrast to IN, development of cancer is not related to lower CD4+ level. With increasing grades of IN and cancer, the proportion of tissues with copy-number abnormalities (CNA) increases, with one of the most common genetic changes being amplification of chromosome 3q. The presence of CNA is associated with the integration of HPV DNA into the host genome, with loss of HPV E2 and/or E2 rearrangement. This suggests a link between CNA and increased HPV-induced chromosomal instability mediated through de-repressed E6 and E7 expression consequent to loss of functional E2 protein. In addition, epigenetic changes occur with increasing frequency in high-grade IN and cancer, such as hypermethylation leading to down-regulation of potential tumor suppressor genes. Analysis of these data together suggests that immune suppression plays a more prominent role in the earlier stages of HPV-associated disease, up to and including incident high-grade IN. Persistent high-grade IN and development of cancer may be more strongly related to the cumulative effect of HPV-associated genetic instability and the resulting host genetic changes. There are few data to suggest a direct role for HIV in the pathogenesis of HPV-associated neoplasia, but HIV-associated attenuation of HPV-specific immune responses may allow for persistence of high-grade IN and sufficient time for accumulation of genetic changes that are important in progression to cancer.


Evolutionary implications of developmental instability in parthenogenetic drosophila mercatorum. I. Comparison of several strains with different genotypes.
Natural populations of sexually reproducing Drosophila mercatorum are capable of a very low rate of parthenogenesis, but this mode of reproduction has apparently never characterized an entirely asexual population in this species. The high abortion rate observed in laboratory parthenogenetic lines suggests that developmental constraints may cause the failure of this trait to spread in nature. To investigate the basis of this developmental instability and how it may affect the evolution of parthenogenesis in natural populations, early embryonic development was compared between one sexual and four parthenogenetic laboratory strains of D. mercatorum. There is a large amount of variation within a given parthenogenetic strain, suggesting that parthenogenesis is associated with a general breakdown of developmental stability. There is relatively little variation among different parthenogenetic strains, suggesting that most abortions are due to a feature inherent to parthenogenetic reproduction rather than a feature of a particular genome. Likewise, there is little variation between parthenogenetic and sexual strains in the causes of abortions, suggesting that the developmental problems encountered by parthenogenetic lineages are not unique to parthenogens. Thus, the failure of parthenogenesis to spread within D. mercatorum can be attributed to no particular developmental constraint per se operating after the initiation of embryogenesis. However, the overall increase in all developmental problems that occurs with the transition from sexual to parthenogenetic development suggests that the high degree of developmental instability associated with parthenogenesis may be considered a developmental constraint in its own right.


Endogenous natural killer cells do not play a role in antitumor effects induced by interleukin-2 in a syngeneic rat colon tumor model.
Previous experiments in a syngeneic rat liver tumor model using the colon adenocarcinoma CC531 demonstrated that injection of interleukin-2 (IL-2) induced significant antitumor responses. Furthermore, it was found that this treatment strategy was accompanied by an increase in the number of natural killer (NK) cells in and around the tumor. In the present study, the role of endogenous NK cells in IL-2-mediated antitumor responses was further elucidated by depleting tumor-bearing rats of NK cells, using the anti-CD161A mouse IgG1 antibody 3.2.3. Rats were depleted either after or prior to tumor induction and subsequently treated with IL-2. The results demonstrated that depletion of NK cells in tumor-bearing rats did not influence IL-2-induced antitumor effects. In addition, injection of IL-2 in NK-cell-depleted rats induced repopulation of NK cells in the peripheral blood from 3 days on and further after the last injection with IL-2. Therefore, the possibility cannot be excluded that de novo recruited NK cells play a role in attaining IL-2 mediated antitumor effects, but NK cells, which were present before or during the start of IL-2 therapy, were not relevant.


Split Cartilage Resection of Nasal Dome: A Solution to Ptotic Nasal Tips.
In ptotic noses, it is rather difficult to achieve the intended functional and cosmetic result without modifying the alar cartilage and creating a new nasal tip. The split cartilage resection method was intended to create a new and permanent nasal tip to protect the physiologic and cosmetic appearance of the nose in the presence of long and ptotic nasal tip. A total of 53 patients who had nasal tip ptosis were included in the study: 26 patients (Group 1) who underwent lateral crural overlap because of the alar cartilage problem and 27 patients (Group 2) who underwent dome split cartilage resection. After at least 1 year of follow-up, the pre- and postoperative measurements of patients indicating their rotations and projections in their computerized images were compared and acoustic rhinometry was performed to determine the nasal valve function. There were no significant differences between the 2 groups with respect to the pre- and postoperative nasolabial angels, rotation angles, Goode index, and nasofacial angle. There were no significant differences between the nasal cavity volume values of the 2 groups; the volume increase in wide nasal cavity in Group 2 was higher. After the operation, the increase in minimum cross-sectional area values in Group 2 was significantly >1 in Group 1. The nasal tip split resection method is a method that can be implemented and should be kept in mind as a technique, which must be considered as an alternative method for noses with ptotic and long nasal tip disorder.


Nanoscale study of cartilage surfaces using atomic force microscopy.
Articulating cartilage wear plays an important role in cartilage degeneration and osteoarthritis (OA) progression. This study investigated the changes of mechanical properties and surface roughness of sheep cartilages with wear progression at a nanometre scale. Young sheep's rear legs were subjected to a series of wear tests to generate worn cartilage samples to simulate the OA progression. Atomic force microscopy (AFM) was used to determine the effective indentation modulus and to measure the surface morphology of moist cartilage surfaces. The study has found that the mean effective indentation modulus values of worn cartilages were lower than that of healthy cartilage as the control sample. A medium-to-strong correlation between the effective indentation modulus values and the OA grades has been found. The relation between surface topography and effective indentation modulus values of the cartilage surfaces with OA progression was weakly correlated. The method established in this study can be implemented to investigate the effective indentation modulus values of clinical osteoarthritic cartilages and to assist in the understanding and assessment of OA.


[Risk factors for prosthesis exposure in treatment of genital prolapse via the vaginal approach].
Prosthetic reinforcement in the surgical repair of pelvic prolapse by the vaginal approach is currently on the increase. However, this technique is not without tolerance-related problems. The most frequently described complication is prosthesis exposure, including erosion and delayed healing. It is independent of a granuloma and a major infection as pelvic cellulitis. Its mechanism is associated with defective vaginal healing. The purpose of our study is to define the risk factors for exposure of the prosthetic material. Two hundred and seventy-seven medical records relating to patients undergoing surgery due to pelvic prolapse were included in our study. The treatment of genital prolapse was managed via the vaginal approach with polypropylene mesh. This is a continuous, retrospective study conducted over a period of 24 months. Thirty-four cases of prosthesis exposure were observed in the 2 months following surgery, which represents an incidence of 12.27%. The risk factors are concomitant hysterectomy [odds ratio 5.17 (P = 0.001)] and inverted T colpotomy [odds ratio 6.06 (P = 0.01)]. The protective factors are preservation of the uterus and the performance of a minor colpotomy in patients who had already undergone a hysterectomy or in those whose uterus had been preserved [odds ratio 5.16 (P = 0.0001)]. In our study, we have only found risk factors of operative protocol. In fact, other information as age, menopause status or medical history of the patient is not significant. The uterus must be preserved and the number and extent of colpotomies needed to insert the prosthesis must be limited.


Oxidative stress as a mediator of cardiovascular disease.
During physiological processes molecules undergo chemical changes involving reducing and oxidizing reactions. A molecule with an unpaired electron can combine with a molecule capable of donating an electron. The donation of an electron is termed as oxidation whereas the gaining of an electron is called reduction. Reduction and oxidation can render the reduced molecule unstable and make it free to react with other molecules to cause damage to cellular and sub-cellular components such as membranes, proteins and DNA. In this paper, we have discussed the formation of reactive oxidant species originating from a variety of sources such as nitric oxide (NO) synthase (NOS), xanthine oxidases (XO), the cyclooxygenases, nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase isoforms and metal-catalysed reactions. In addition, we present a treatise on the physiological defences such as specialized enzymes and antioxidants that maintain reduction-oxidation (redox) balance. We have also given an account of how enzymes and antioxidants can be exhausted by the excessive production of reactive oxidant species (ROS) resulting in oxidative stress/nitrosative stress, a process that is an important mediator of cell damage. Important aspects of redox imbalance that triggers the activity of a number of signalling pathways including transcription factors activity, a process that is ubiquitous in cardiovascular disease related to ischemia/reperfusion injury have also been presented.


Patterns of Relapse after Definitive Chemoradiotherapy in Stage II/III (Non-T4) Esophageal Squamous Cell Carcinoma.
The purpose of this study was to investigate the utility of surveillance after definitive chemoradiotherapy (dCRT) in patients with squamous cell carcinoma. Patients who underwent dCRT for stage II/III (excluding T4) esophageal squamous cell carcinoma were analyzed. First failures following complete response were classified into luminal relapse (LR), regional relapse (RR), distant metastasis (DM), new cancer diagnosed by esophagogastroduodenoscopy (NC-E), and new cancer other than NC-E (NC-O). We focused on LR, RR, and NC-E, and analyzed their frequency, timings and survival outcomes after local treatments. Among 302 patients treated with dCRT, 204 achieved complete response. The number of patients who recurred with LR, RR, DM, NC-E, and NC-O were 28 (14% of 204), 13 (6%), 39 (19%), 34 (17%), and 16 (8%). Ninety-three percent of LRs were diagnosed within 3 years after dCRT, and all RRs were diagnosed within 2 years. Annual odds of NC-E did not decrease over time. Twenty-three patients with LR, 6 with RR, and 32 with NC-E underwent local treatment, and their median overall survivals were 49.2, 19.5, and 108.9 months. Surveillance with esophagogastroduodenoscopy may be important in the first 3 years after dCRT to detect LR and to detect NC-E beyond 3 years.


Limited maternal fuel availability due to hyperinsulinemia retards fetal growth and development in the rat.
We rendered pregnant rats chronically hyperinsulinemic to determine the effect of reduced maternal metabolic fuel availability on fetal growth and development. We implanted osmotically driven insulin loaded minipumps on day 14 (term 21.5 days) in pregnant rats. This significantly increased maternal plasma concentrations of insulin and reduced glucose from day 15 until term. From day 17 until birth, fetal growth was significantly less for hyperinsulinemic mothers (term birth weight 4.53 +/- 0.07 versus 5.64 +/- 0.06 g, p less than 0.001). In fetuses of hyperinsulinemic mothers plasma glucose and insulin concentrations were significantly reduced while glucagon concentrations were increased. Total plasma amino acids were significantly reduced in maternal rats and their fetuses from days 17 to 19 while arteriovenous blood gas tensions and pH did not differ between fetuses of hyperinsulinemic and control mothers. Small for gestational age newborn pups of hyperinsulinemic mothers were hypoglycemic for the first 240 min of life as a result of limited hepatic glycogen stores and a delay in the normally expected induction of hepatic cytosolic phosphoenolpyruvate carboxykinase. This occurred despite significant increases in neonatal plasma glucagon concentrations. These data indicate that limitation of maternal glucose and amino acids with normal placental gaseous exchange retards fetal growth, limits hepatic glycogen deposition, and delays neonatal phosphoenolpyruvate carboxykinase induction. Limited fetal insulin secretion resulting from diminished maternal fuel availability may have also been a factor in retarding growth. The delay in phosphoenolpyruvate carboxykinase induction despite enhanced glucagon secretion during fetal and neonatal life suggests a specific "resistance" to this hormone in the rat growth retarded by limited metabolic fuel availability.


Herpes simplex virus infections of the central nervous system. Encephalitis and neonatal herpes.
Herpes simplex virus (HSV) infections are among the most commonly encountered in humans. Fortunately, the resulting diseases are more usually nuisances, such as recurrent fever blisters, rather than life threatening or morbidity inducing. Nevertheless, HSV can result in disease of the central nervous system (CNS) with attendant neurological complications. Examples of the latter include herpes simplex encephalitis (HSE) or neonatal HSV infection. The past decade has witnessed significant advances in our understanding of the pathogenesis of these 2 forms of disease and, even more importantly, their amenability to treatment. This review summarises our current understanding of the natural history, pathogenesis, presentation, and treatment of HSV infections of the CNS. Because of the life-threatening nature of herpes simplex infections of the CNS, particular attention is paid to clinical presentation and differential diagnosis of confounding entities which mimic herpes simplex encephalitis. The controversy of brain biopsy versus alternative noninvasive diagnostic procedures is discussed. Clinical presentation and, importantly, the lack of uniform clinical presentation, as well as the value of intervention with appropriate antiviral drugs such as aciclovir and vidarabine (adenine arabinoside, ara-A), are stressed. The clinical outcome of herpes simplex virus infections of the CNS with therapy is particularly relevant. In spite of early intervention with selective and specific inhibitors of viral replication, return to normal function is not always achieved. At the conclusion of this review, the reader should be aware of the potential value of therapy as well as the problems encountered with diagnosis and management of patients with herpes simplex virus infections of the CNS.


Geotechnical engineering properties of incinerator ash mixes.
The incineration of solid waste produces large quantities of bottom and fly ash. Landfilling has been the primary mode of disposal of these waste materials. Shortage in landfill space and the high cost of treatment have, however, prompted the search for alternative uses of these waste materials. This study presents an experimental program that was conducted to determine the engineering properties of incinerator ash mixes for use as construction materials. Incinerator ash mixes were tested as received and around optimum compacted conditions. Compaction curves, shear strength, and permeability values of fly ash, bottom ash, and their various blends were investigated. Bottom ash tends to achieve maximum dry density at much lower water content than does fly ash. The mixes displayed a change in their cohesion and friction angle values when one of the two mix components was altered or as a result of the addition of water. The permeability of bottom ash is quite comparable to that of sand. The permeability of fly ash lies in the range of those values obtained for silts and clays. A 100% bottom ash compacted at the optimum water content has a lower density value and yields a higher friction angle and cohesion values than most construction fills. This would encourage the use of bottom ash as a fill or embankment material because free drainage of water will prevent the buildup of pore water pressures.


Erectile dysfunction and exposure to ambient Air pollution in a nationally representative cohort of older Men.
Little is known about the association between air pollution and erectile dysfunction (ED), a disorder occurring in 64% of men over the age of 70, and to date, no studies have been published. To address this significant knowledge gap, we explored the relationship between ED and air pollution in a group of older men who were part of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort study of older Americans. We obtained incident ED status and participant data for 412 men (age 57-85). Fine particulate matter (PM2.5) exposures were estimated using spatio-temporal models based on participants' geocoded addresses, while nitrogen dioxide (NO2) and ozone (O3) concentrations were estimated using nearest measurements from the Environmental Protection Agency's Air Quality System. The association between air pollution and incident ED (newly developed in Wave 2) was examined and logistic regression models were run with adjusted models controlling for race, education, season, smoking, obesity, diabetes, depression, and median household income of census tract. We found positive, although statistically insignificant, associations between PM2.5, NO2, and O3 exposures and odds of incident ED for each of our examined exposure windows, including 1 to 7 year moving averages. Odds ratios (OR) for 1 and 7 year moving averages equaled 1.16 (95% CI: 0.87, 1.55) and 1.16 (95% CI: 0.92, 1.46), respectively, for an IQR increase in PM2.5 exposures. Observed associations were robust to model specifications and were not significantly modified by any of the examined risk factors for ED. We found associations between PM2.5, NO2, and O3 exposures and odds of developing ED that did not reach nominal statistical significance, although exposures to each pollutant were consistently associated with higher odds of developing ED. While more research is needed, our findings suggest a relationship between air pollutant exposure and incident cases of ED, a common condition in older men.


Using Photovoice, Latina Transgender Women Identify Priorities in a New Immigrant-Destination State.
Little is known about the immigrant Latino/a transgender community in the southeastern United States. This study used photovoice, a methodology aligned with community-based participatory research, to explore needs, assets, and priorities of Latina transgender women in North Carolina. Nine immigrant Latina male-to-female transgender women documented their daily experiences through photography, engaged in empowerment-based photo-discussions, and organized a bilingual community forum to move knowledge to action. From the participants' photographs and words, 11 themes emerged in three domains: daily challenges (e.g., health risks, uncertainty about the future, discrimination, and anxiety about family reactions); needs and priorities (e.g., health and social services, emotional support, and collective action); and community strengths and assets (e.g., supportive individuals and institutions, wisdom through lived experiences, and personal and professional goals). At the community forum, 60 influential advocates, including Latina transgender women, representatives from community-based organizations, health and social service providers, and law enforcement, reviewed findings and identified ten recommended actions. Overall, photovoice served to obtain rich qualitative insight into the lived experiences of Latina transgender women that was then shared with local leaders and agencies to help address priorities.


Small-Bowel Capsule Endoscopy-Optimizing Capsule Endoscopy in Clinical Practice.
The small bowel is the longest organ within the gastrointestinal tract. The emergence of small bowel capsule endoscopy (SBCE) over the last 20 years has revolutionized the investigation and diagnosis of small bowel pathology. Its utility as a non-invasive and well-tolerated procedure, which can be performed in an outpatient setting, has made it a valuable diagnostic tool. The indications for SBCE include obscure gastrointestinal bleeding, small bowel Crohn's disease, and, less frequently for screening in polyposis syndromes, celiac disease, or other small bowel pathology. Currently, there are several small bowel capsules on the market from different manufacturers; however, they share many technological features. The European Society of Gastrointestinal Endoscopy (ESGE) only recently developed a set of key quality indicators to guide quality standards in this area. Many of the technical aspects of capsule endoscopy still feature a degree of uncertainty in terms of optimal performance. Incomplete studies due to slow transit through the bowel, poor imaging secondary to poor preparation, and the risk of capsule retention remain frustrations in its clinical utility. Capsule review is a time-consuming process; however, artificial intelligence and machine learning offer opportunities to improve this. This narrative review examines our current standing in a number of these aspects and the potential to further the application of SBCE in order to maximize its diagnostic utility.


Mobile Phone Use, Emotion Regulation, and Well-Being.
This study examined the use of mobile phones to regulate negative emotions, considering both the role of different aspects of phone use and individual differences in emotion regulation strategies. A total of 287 young adult smartphone users completed an online survey that addressed use of mobile phones for negative emotion regulation. They responded to a phone loss scenario by rating how much they would miss various uses/functions of the phone (which could be involved in emotion regulation). Habitual use of reappraisal to regulate emotion was associated with missing both interpersonal contact and social support, but not access to entertainment/information. In contrast, habitual use of emotion suppression was associated only with missing entertainment/information content. Regulating negative emotions via mobile phone was associated with missing all three uses/functions of the phone, but perception that the phone was effective in remediating negative emotion was associated only with missing social support. Well-being was related to greater use and perceived effectiveness of the mobile phone for emotion regulation. Overall, this study demonstrates that mobile phones can yield psychological benefits, depending on how they are used. Findings suggest that using the phone for social support is most likely to lead to effective remediation of negative emotion. Interpretations and implications of the findings are discussed.


Prenatal diagnosis of major aortopulmonary collateral arteries (MAPCA) in fetuses with pulmonary atresia with ventricular septal defect and agenesis of ductus arteriosus.
The aim of this study was to describe the prenatal diagnosis of Major Aortopulmonary Collateral Arteries (MAPCAs), and to present a systematic ultrasound method for evaluating lung vascularity in fetuses with pulmonary atresia with ventricular septal defect (PAVSD) and agenesis of ductus arteriosus (DA). This retrospective study evaluated fetuses diagnosed with PAVSD with agenesis of DA, for the presence of the MAPCAs anomaly. Fetal pulmonary vasculature was investigated by 2D and 4D Spatio Temporal Image Correlation (STIC) technology using High Definition Color Doppler. Over a 10 year period, six fetuses were diagnosed with MAPCAs. Prenatal diagnosis was made between 17 w 6 d and 28 w 4 d in five fetuses, with the sixth diagnosed at 37 w 6 d. All six had PAVSD with agenesis DA, four exhibited pulmonic atresia without any arterial outflow, while two fetuses presented with absent left pulmonary artery, and a miniscule right pulmonary artery. In five cases, the parents elected to terminate the pregnancy and the last, although born alive, did not survive an attempt at restorative surgery and died at the age of 5 months. Postnatal CT angiography imaging of this case revealed the subclavian origin of the MAPCAs. Chromosomal micro array analysis of the amniotic fluid revealed that five of the six fetuses were normal and one was lost to follow up. MAPCAs should be investigated in cases of PAVSD with agenesis DA. A meticulous ultrasound evaluation using 2D and 4D STIC can permit the prenatal diagnosis of this anomaly and provide the parents with the opportunity for prenatal consultation.


[Open laser surgery on the locomotor apparatus].
The first applications of laser in surgery of the locomotor apparatus in the early 1980s used the haemostatic properties of laser to diminish the amount of substitution of coagulation factors in haemophiliac patients. Only since the early 1990s has a device been available in corporating the pulsed holmium:YAG laser which works in a fluid medium without relevant side effects. Apart from haemostasis, the cutting function and tissue ablation, together with the thermal shrinking effect, are exploited in arthroscopy and percutaneous disc decompression. Now that the biophysical mechanisms of action have been elucidated, nothing stands in the way of the use of infrared lasers in open surgery of the locomotor apparatus in some indications. In a prospective clinical study we included 30 consecutive patients who underwent open laser surgery from November 1992 to August 1994, for the following indications: the sparing haemostatic tissue ablation was used for synovectomy or for bony resection in osteophytes and osteochondromas of different locations, an osteoid osteoma and a painful sacral hyperplasia in the presence of incomplete sacral meningomyelocele. With bleeding eliminated, the shaping was much easier. The non-ablative shrinking produced less tissue loss and a stabilizing strengthening of tissue at the margins of soft tissue resections, e.g. in jumper's knee, tennis elbow and Achilles tendon cysts. All laser functions that are useful in open surgery have also been used in sequestered disc herniations that are inaccessible a percutaneous procedure and, in spinal decompression, for remodelling of the posterior spine contour. An analgesic effect of laser limited the postoperative administration of analgesic drugs to an average of 3 days. No complications related to the laser treatment were observed. At follow-up 12-21 months after operation, 25 of the 30 patients in this heterogeneous population showed complete or near-total healing of the operated pathological finding, and a further 3 patients showed significant improvement. To what extent these very encouraging results will persist will be shown by long-term observation.


Correlation between immune maturation and idiotypic network recognition.
The maturation of T-dependent humoral immune responses is mediated by somatic mutations. Antigen selection is one mechanism for the activation of B cell clones which express antibodies with progressively increased affinity and which are derived as somatic variants from germ-line-encoded genes. However, the emergence of B cell clones secreting rather low-affinity antibodies and the shift to alternative germ-line V region gene combinations during secondary and tertiary responses cannot be explained by antigen selection. It has been considered that idiotypic suppression may favor this clonal shift. Such an involvement would require that idiotypic recognition in the syngeneic host must be highly restricted to private idiotopes of each clone sequentially activated during immune maturation. To test this possibility, we produced 19 syngeneic anti-idiotypic antibodies to the germ-line-encoded major Ox1 idiotype (IgM-IdOx1 H11.5) of the anti-2-phenyl-oxazolone (phOx) immune response in BALB/c mice. The fine specificity of these anti-IdOx1 was tested with a set of anti-phOx monoclonal antibodies, representing the first steps of maturation. About half of the anti-IdOx1 showed almost no reactivity with the IdOx1 after the switch to IgG and none of the anti-IdOx1 reacted with anti-phOx antibodies which carried a glycine or histidine instead of arginine as the middle amino acid of the D region. These observations suggest a strong correlation between immune maturation and the idiotypic network. A model is presented in which idiotypic suppression may function as a driving force for diversification and maturation of the antigen-induced immune response.


Structural and Thermal Properties of Ethylene-Norbornene Copolymers Obtained Using Vanadium Homogeneous and SIL Catalysts.
The series of ethylene-norbornene (E-NB) copolymers was obtained using different vanadium homogeneous and supported ionic liquid (SIL) catalyst systems. The 13C and 1H NMR (carbon and proton nuclear magnetic resonance spectroscopy) together with differential scanning calorimetry (DSC) were applied to determine the composition of copolymers such as comonomer incorporation (CNB), monomer dispersity (MD), monomer reactivity ratio (re), sequence length of ethylene (le) and tetrad microblock distributions. The relation between the type of catalyst, reaction conditions and on the other hand, the copolymer microstructure, chain termination reaction analyzed by the type of unsaturation are discussed. In addition, the thermal properties of E-NB copolymers such as the melting and crystallization behavior, like also the heterogeneity of composition described by successive the self-nucleation and annealing (SSA) and the dispersity index (DI) were determined.


Effect of Fc Fusion on Folding and Immunogenicity of Middle East Respiratory Syndrome Coronavirus Spike Protein.
Middle East respiratory syndrome coronavirus (MERS-CoV) induces severe respiratory impairment with a reported mortality rate of ~36% in humans. The absence of clinically available MERS-CoV vaccines and treatments to date has resulted in uncontrolled incidence and propagation of the virus. In vaccine design, fusion with the IgG Fc domain is reported to increase the immunogenicity of various vaccine antigens. However, limited reports have documented the potential negative effects of Fc fusion on vaccine antigens. To determine whether Fc fusion affects the immunogenicity of MERS-CoV antigen, we constructed a Fcassociated MERS-CoV spike protein (eS770-Fc, 110 kDa), whereby human IgG4 Fc domain was fused to MERS-CoV spike protein (eS770) via a Gly/Pro linker using baculovirus as the expression system. For comparative analyses, two eS770 proteins lacking the IgG4 Fc domain were generated using the IdeS protease (eS770-ΔFc) or His tag attachment (eS770-His) and the immunogenicity of the above constructs were examined following intramuscular immunization in mice. Contrary to expectations, non-Fc spike proteins (eS770-ΔFc, eS770-His; 90 kDa) showed higher immunogenicity than the Fc fusion protein (eS770-Fc). Moreover, unlike non- Fc spike proteins, eS770-Fc immunization did not elicit neutralizing antibodies against MERSCoV. The lower immunogenicity of Fc-fused eS770 was related to alterations in the structural conformation of the spike protein. Taken together, our results indicate that IgG Fc fusion reduces the immunogenicity of eS770 by interfering with the proper folding structure.


Effect of exercise-induced dehydration on circulatory markers of oxidative damage and antioxidant capacity.
Dehydration is a common event associated with exercise. However, few studies have examined the effects of dehydration on plasma redox status in humans. Eighty-two athletes were recruited and baseline anthropometrics and blood samples were obtained. Athletes then engaged in a dehydration protocol, training until 3% of preweight body mass was lost. Athletes returned to the lab and had postdehydration blood collected. Athletes then consumed an isotonic drink until pre-exercise body weight was reestablished. Blood was then recollected (1 h post full rehydration (PFR)). Samples were centrifuged and the plasma snap frozen in liquid nitrogen and stored at -80 °C. Lipid and protein oxidative stress was determined by measuring F2-isoprostanes and protein carbonyls (PC), respectively. Antioxidant capacity was determined by the ferric reducing ability of plasma (FRAP) and trolox equivalent antioxidant capacity (TEAC) assays. Plasma osmolality was determined using an osmometer. Statistical analysis utilized a 1-way ANOVA with posthoc testing. Values are reported as mean ± SD. Plasma osmolality was significantly elevated immediately postdehydration (p ≤ 0.001) but decreased to baseline at PFR. Plasma TEAC increased immediately postdehydration and at PFR (p ≤ 0.001). FRAP increased immediately postdehydration (p ≤ 0.001) and decreased to below baseline at PFR (p ≤ 0.05). Conversely, F2-isoprostanes declined significantly from baseline to immediately postdehydration and then significantly rose at PFR (p ≤ 0.001), whereas PC declined at PFR (p ≤ 0.01). This study indicates that dehydration and exercise cause a significant increase in plasma osmolality and antioxidant potential immediately postexercise. We propose dehydration significantly elevates antioxidant concentration which suppresses F2-isoprostanes and PC.


Functional characterization of an unknown soybean intrinsically disordered protein in vitro and in Escherichia coli.
Intrinsically disordered proteins (IDPs) possess a wide range of biological function in all organisms, however the specific functions of most IDPs are still unknown. Soybean LOC protein, LOC for short, is a heat-stable protein, which is more abundant in the stress-resistant radicles. Sequence alignment and phylogenetic analysis showed that LOC is a functionally unknown protein and conserved in Fabaceae. LOC, being enriched in most disorder-promoting residues and depleted in most order-promoting residues, was predicted to contain high levels of intrinsic disorder by several commonly used computational tools. However, it was also predicted to contain two disorder-based protein-protein binding sites and two short α-helical segments. The circular dichroism spectroscopic analysis showed that this protein is mostly disordered in water, but can form more α-helical structure in the presence of SDS and TFE. Functional in vitro studies showed that the LOC protein is able to prevent lactate dehydrogenase inactivation by freeze-thaw at a molar ratio of 10:1. Furthermore, in vivo analyses revealed the survival rate of Escherichia coli over-expressing LOC protein under the conditions of osmotic stress was noticeably increased in comparison with the control. These observations suggest that the intrinsically disordered protein LOC might serve as a chaperone and/or cell protector.


Beyond the Microbiome: Germ-ganism? An Integrative Idea for Microbial Existence, Organization, Growth, Pathogenicity, and Therapeutics.
The advances made by microbiome research call for new vocabulary and expansion of our thinking in microbiology. For example, the life-forms presenting in both unicellular and multicellular formats invite us to rethink microbial existence, organization, growth, pathogenicity, and therapeutics in the 21st century. A view of such populations as parts of single organisms with a loose, distributed multicellular organization, introduced here as a germ-ganism, rather than communities, might open up interesting prospects for diagnostics and therapeutics innovation. This study tested and further contextualized the concept of germ-ganism using solid cultures of bacteria and fungi. Based on our findings and the literature reviewed herein, we propose that germ-ganism has synergy with a systems medicine approach by broadening host-environment interactions from cells and microorganisms to a scale of biological ecosystems. Germ-ganism also brings about the possibility of studying the multilevel impacts of novel therapeutic agents within and across networks of microbial ecosystems. The germ-ganism would lend itself, in the long term, to a veritable biocybernetics system, while in the mid-term, we anticipate it will contribute to new diagnostics and therapeutics. Biosecurity applications would be immensely affected by germ-ganism. Industrial applications of germ-ganism are of interest as a more sustainable alternative to costly solutions such as tampered strains/microorganisms. In conclusion, germ-ganism is informed by lessons from microbiome research and invites rethinking microbial existence, organization, and growth as an organism. Germ-ganism has vast ramifications for understanding pathogenicity, and clinical, biosecurity, and biotechnology applications in the current historical moment of the COVID-19 pandemic and beyond.


Forebrain projections to brainstem nuclei involved in the control of mandibular movements in rats.
Mandibular movements occur through the triggering of trigeminal motoneurons. Aberrant movements by orofacial muscles are characteristic of orofacial motor disorders, such as nocturnal bruxism (clenching or grinding of the dentition during sleep). Previous studies have suggested that autonomic changes occur during bruxism episodes. Although it is known that emotional responses increase jaw movement, the brain pathways linking forebrain limbic nuclei and the trigeminal motor nucleus remain unclear. Here we show that neurons in the lateral hypothalamic area, in the central nucleus of the amygdala, and in the parasubthalamic nucleus, project to the trigeminal motor nucleus or to reticular regions around the motor nucleus (Regio h) and in the mesencephalic trigeminal nucleus. We observed orexin co-expression in neurons projecting from the lateral hypothalamic area to the trigeminal motor nucleus. In the central nucleus of the amygdala, neurons projecting to the trigeminal motor nucleus are innervated by corticotrophin-releasing factor immunoreactive fibers. We also observed that the mesencephalic trigeminal nucleus receives dense innervation from orexin and corticotrophin-releasing factor immunoreactive fibers. Therefore, forebrain nuclei related to autonomic control and stress responses might influence the activity of trigeminal motor neurons and consequently play a role in the physiopathology of nocturnal bruxism.


Contact lens-induced regression of Lisch epithelial corneal dystrophy.
To describe the use of soft contact lenses (CL) to reduce the epithelial opacities of Lisch epithelial corneal dystrophy (LECD). First presentation of confocal microscopy in LECD. Two unrelated female patients with LECD demonstrated a central gray opacity with distinct visual impairment. The first patient wore a daily hydroxyethlmethacrylate (HEMA) CL for 3 months and the second, a daily silicone hydrogel CL for 1 month. Pre-CL and post-CL appearances of the cornea were photodocumented at the slit lamp. Additionally, in the second patient, a confocal microscopic evaluation of LECD was performed. In both patients, the wearing of CL resulted in a distinct reduction of central corneal opacification with a visual improvement. Discontinued wearing of CL induced again a progression of opacity. The confocal microscopy disclosed the typical intracytoplasmatic vacuolization of the involved epithelial cells. Wearing CL for a longer duration causes a significant regression of corneal opacities in LECD. The etiology of this phenomenon is interpreted as a CL-induced thinning of corneal epithelium and reduction of epithelial layers.


The other side of the coin: impact of toxin generation and nutrition on the uremic syndrome.
Both the morbidity of the uremic syndrome and the generation of uremic toxins are attributed to malnutrition. If protein intake and catabolism result in the generation of solutes, then nutritional intake should be related directly to toxicity. On the other hand, inadequate nutrition has been linked to inflammation and mortality. It remains difficult to reconcile these two lines of thought. Several possibilities exist that might account for this apparent paradox: 1) not all nutritional and protein degradation products are toxic; 2) toxins generated from increased protein intake are removed if protein intake is linked to dialysis dose; 3) albumin acts as a buffer for toxicity-hypoalbuminemia favors liberation of protein-bound toxins from their binding sites, enhancing their toxicity; 4) solutes generated from tissue breakdown are more toxic than those generated by nutritional protein; 5) both high and low concentrations of solutes have a negative impact; 6) toxic compounds unrelated to protein breakdown are specific causes of malnutrition and inflammation; 7) and/or residual renal function plays a key role in the elimination of compounds discussed under possibility 6. Thus the uremic syndrome should be considered as a potentially fatal interaction among inflammation, malnutrition, low levels of albumin in the plasma, accumulated protein-bound solutes and generation of nonnutritionally related toxins. Not only optimal dialysis, but also optimal nutritional intake and optimal utilization of these nutrients should help neutralize this chain of events.


Sudden cardiac death in hypertrophic cardiomyopathy.
Sudden death is an important facet of the natural history of hypertrophic cardiomyopathy. Issues related to the nature and etiology of sudden death and the prospective identification of those patients at increased risk have been the subject of intense study, and consequently, our concepts and knowledge have continued to evolve. Occurrence of sudden death has been reported to be about 2-3% per year in a hospital-based referral population and, although described in most age groups, is most common in older children and young adults. The typical profile is that of a young asymptomatic patient with substantially increased left ventricular wall thickness who dies while performing sedentary or modest physical activities; however, a substantial minority die suddenly during or just after severe exertion, including those participating in competitive athletics. Other risk factors that have been identified in patients with hypertrophic cardiomyopathy include nonsustained ventricular tachycardia on ambulatory electrocardiogram, a strong family history of sudden death, and prior occurrence of syncope (or cardiac arrest). Electrophysiological studies have shown that most patients judged at increased risk for sudden death have sinoatrial or His-Purkinje conduction disease or inducible supraventricular or ventricular tachycardia; inducibility of a sustained ventricular arrhythmia is associated with prior occurrence of syncope or cardiac arrest. Hemodynamic and electrophysiological studies in patients with hypertrophic cardiomyopathy have demonstrated several potential mechanisms for cardiac arrest or sudden death, including atrial arrhythmias associated with hypotension, bradyarrhythmias, and ventricular tachyarrhythmias, all of which can be exacerbated in the presence of left ventricular outflow tract obstruction or myocardial ischemia.


Rapid analysis of iron concentrates by x-ray fluorescence spectrometry with sol-gel sample preparation technology.
A rapid method for the analysis of iron concentrates by gel sample preparation and x-ray fluorescence (XRF) spectrometry detection was developed. The solution digested by aqua regia was mixed with agarose, and then agarose was dissolved in the boiling solution and the mixture became quasi-solid gel at ambient temperature. The quasi-solid gel was detected by XRF. Analytical characteristics of the methods used were compared, and their reliability were tested against several certified reference materials of iron concentrates. The relative standard deviation was less than 0.3%.


Labor contractors: a conceptual overview.
"The purpose of this paper is to provide an overview of labor brokering or contracting that helps to explain why employers turn to foreign workers to fill certain vacant jobs, and how the presence of foreign workers brought to a country by labor contractors can affect the size and duration of migration flows. The major conclusion is that East Asian policies that aim to avoid the settlement of unskilled foreign workers also make labor brokering a prominent feature of labor migration and migrant labor markets in the region."


[Interplay between defenses and coping during the course of illness--a study of Crohn disease patients].
The psychological coping concept and the psychoanalytic theory of defense are the two most important models for assessing coping with chronic illness. Their interplay has hardly been investigated so far. A "layer model" is proposed to describe the connections between defense and coping. This model is empirically tested by applying a path analysis (latent trait model) to patients suffering from Crohn's disease during the course of the illness. The layer model can be verified, but is valid only during the acute phase of the illness. The results convincingly show that the relationship between defense and coping can only be described as a dynamic interplay that changes in the course of the disease process.


Storm clouds ahead.
The funding squeeze of 2011 will worsen this year, with experts predicting even tighter spending restrictions up to 2014 and beyond. As teams are downgraded and nursing jobs lost, patients could miss out on expert care.


Phylogeny of the teashirt-related zinc finger (tshz) gene family and analysis of the developmental expression of tshz2 and tshz3b in the zebrafish.
The tshz genes comprise a family of evolutionarily conserved transcription factors. However, despite the major role played by Drosophila tsh during the development of the fruit fly, the expression and function of other tshz genes have been analyzed in a very limited set of organisms and, therefore, our current knowledge of these genes is still fragmentary. In this study, we perform detailed phylogenetic analyses of the tshz genes, identify the members of this gene family in zebrafish and describe the developmental expressions of two of them, tshz2 and tshz3b, and compare them with meis1, meis2.1, meis2.2, pax6a, and pax6b expression patterns. The expression patterns of these genes define a complex set of coexpression domains in the developing zebrafish brain where their gene products have the potential to interact.


Effect of water stress on proline synthesis from radioactive precursors.
Barley (Hordeum vulgare L. var. Prior) leaves converted more (14)C-glutamic acid to free proline when water-stressed than when turgid; neither decreased protein synthesis nor isotope trapping by the enlarged free proline pools found in wilted tissue seemed to account for the result. This apparent stimulation of proline biosynthesis in wilted leaves was not observed when radioactive ornithine or P5C (Delta(1)-pyrroline-5-carboxylate, an intermediate following glutamate in proline synthesis) were used as proline precursors unless proline levels were high as a result of previous water stress. We interpret this to mean that any stimulation of proline synthesis by water stress must act on P5C formation rather than its reduction to proline. Experiments showing greater apparent conversion of (14)C-glutamate to proline do not unequivocally prove that proline synthesis is stimulated by water stress, as P5C feeding studies show that proline oxidation is inhibited under comparable conditions. This inhibition could account, at least in part, for increased proline labeling, and must be considered an alternate possibility.


Preserving the emetic effect of syrup of ipecac with concurrent activated charcoal administration: a preliminary study.
Activated charcoal is reported to block the emetic effect of syrup of ipecac. Therefore, activated charcoal administration is commonly delayed until syrup of ipecac induced emesis is complete. The advantages of early administration of activated charcoal have been well documented. Preservation of the emetic effect of syrup of ipecac in the presence of activated charcoal may produce a synergistic effect by enhancing toxin elimination. A study was conducted in ten human volunteers to determine if activated charcoal prevents the emetic effect of syrup of ipecac when a temporal separation exists between administration of the two substances. Syrup of ipecac 60 ml plus water 480 ml was administered via an 18 French nasogastric tube followed by an aqueous slurry of activated charcoal 50 g five minutes later. Eight (80%) of the subjects had emesis in a mean time of 20.25 minutes (range 16-26 min). The total dose of activated charcoal was retained for a mean time of 6.75 minutes (range 0-17 min). Two subjects (20%) failed to have emesis. This study illustrates that activated charcoal may not completely block the emetic effect of syrup of ipecac.


Production, crystallization and preliminary X-ray diffraction analysis of the allergen Can f 2 from Canis familiaris.
The allergen Can f 2 from dog (Canis familiaris) present in saliva, dander and fur is an important cause of allergic sensitization worldwide. Here, the production, isolation, crystallization and preliminary X-ray diffraction analysis of two crystal forms of recombinant Can f 2 are reported. The first crystal form belonged to space group C222, with unit-cell parameters a = 68.7, b = 77.3, c = 65.1 A, and diffracted to 1.55 A resolution, while the second crystal form belonged to space group C2, with unit-cell parameters a = 75.7, b = 48.3, c = 68.7 A, beta = 126.5 degrees , and diffracted to 2.1 A resolution. Preliminary data analysis indicated the presence of a single molecule in the asymmetric unit for both crystal forms.


A highly selective 2''-O-glycosyltransferase from Ziziphus jujuba and De novo biosynthesis of isovitexin 2''-O-glucoside.
A novel and efficient 2''-O-glycosyltransferase ZjOGT38 was identified from Ziziphus jujuba. It could regio-selectively glycosylate 2-hydroxyflavanone C-glycosides. ZjOGT38 allowed de novo biosynthesis of isovitexin 2''-O-glucoside in E. coli.


Efficacy and safety of biofilm dispersal by glycoside hydrolases in wounds.
Novel anti-biofilm and dispersal agents are currently being investigated in an attempt to combat biofilm-associated wound infections. Glycoside hydrolases (GHs) are enzymes that hydrolyze the glycosidic bonds between sugars, such as those found within the exopolysaccharides of the biofilm matrix. Previous studies have shown that GHs can weaken the matrix, inducing bacterial dispersal, and improving antibiotic clearance. Yet, the number of GH enzymes that have been examined for potential therapeutic effects is limited. In this study, we screened sixteen GHs for their ability to disperse mono-microbial and polymicrobial biofilms grown in different environments. Six GHs, α-amylase (source: A. oryzae), alginate lyase (source: various algae), pectinase (source: Rhizopus sp.), amyloglucosidase (source: A. niger), inulinase (source: A. niger), and xylanase (source: A. oryzae), exhibited the highest dispersal efficacy in vitro. Two GHs, α-amylase (source: Bacillus sp.) and cellulase (source: A. niger), used in conjunction with meropenem demonstrated infection clearing ability in a mouse wound model. GHs were also effective in improving antibiotic clearance in diabetic mice. To examine their safety, we screened the GHs for toxicity in cell culture. Overall, there was an inverse relationship between enzyme exposure time and cellular toxicity, with twelve out of sixteen GHs demonstrating some level of toxicity in cell culture. However, only one GH exhibited harmful effects in mice. These results further support the ability of GHs to improve antibiotic clearance of biofilm-associated infections and help lay a foundation for establishing GHs as therapeutic agents for chronic wound infections.


[High molecular weight tau proteins and acquisition of neuronal polarity in peripheral nervous system].
Several variants of the microtubule-associated tau proteins, are expressed during brain development and in adulthood. These entities are required to define the polarity of the neuron and the architecture of the axon but differ in sequence and in their microtubule polymerizing activity. Here, we describe a new group of high molecular weight tau proteins that contain one or two additional exons of 711 and 198 bp in their middle region and a variable N-terminal domain. These high molecular weight tau variants are preferentially expressed in the peripheral nervous system. Immunohistochemical studies showed that they are also present in the dorsal horn of the spinal cord where they are probably transported by sensory fibers arising in the periphery. However, a minor fraction of these proteins is present in the motor neurons of the ventral horn. Similar studies were performed with the neuroblastoma N115 cell line which can be differentiated in vitro and expresses only high molecular weight tau forms. In the non differentiated cells, tau antibodies label the domain of the cell body localized around the centrosome whereas, after differentiation, the cell process facing this structure is also stained. These data suggest that axonal polarity is predetermined by the localization of tau proteins in the domain of the cell body defined by the centrosome.


Purpura fulminans in meningococcal septicaemia in an adult: a case report.
Purpura fulminans is a rare and severe complication of meningococcal septicaemia. It presents as a petechial rash spreading rapidly in extent and depth, evolving into full-thickness skin necrosis. The condition is extremely uncommon in the adult population. We report the case of a 28-yr-old man with extensive meningococcal-related skin necrosis. The initial diagnosis was made and first treatment given in the emergency department of a local hospital, from where after 12 days he was transferred to our hospital. Our approach was based on the continuation of intensive treatment and on staged aggressive debridement. Temporary alloplastic skin grafts were used to prepare the wound bed and the wounds were closed with autologous skin grafts. The patient survived but subsequently, owing to chronic skin ulceration and scar instability, he underwent late bilateral below-the-knee amputation.The patient returned to normal deambulation with an orthopaedic prosthesis 18 months after the onset of meningococcal septicaemia.


Estimating the hemodynamic influence of variable main body-to-iliac limb length ratios in aortic endografts.
We conducted a computational study to assess the hemodynamic impact of variant main body-to-iliac limb length (L1/L2) ratios on certain hemodynamic parameters acting on the endograft (EG) either on the normal bifurcated (Bif) or the cross-limb (Cx) fashion. A customary bifurcated 3D model was computationally created and meshed using the commercially available ANSYS ICEM (Ansys Inc., Canonsburg, PA, USA) software. The total length of the EG, was kept constant, while the L1/L2 ratio ranged from 0.3 to 1.5 in the Bif and Cx reconstructed EG models. The compliance of the graft was modeled using a Fluid Structure Interaction method. Important hemodynamic parameters such as pressure drop along EG, wall shear stress (WSS) and helicity were calculated. The greatest pressure decrease across EG was calculated in the peak systolic phase. With increasing L1/L2 it was found that the Pressure Drop was increasing for the Cx configuration, while decreasing for the Bif. The greatest helicity (4.1 m/s2) was seen in peak systole of Cx with ratio of 1.5 whereas its greatest value (2 m/s2) was met in peak systole in the Bif with the shortest L1/L2 ratio (0.3). Similarly, the maximum WSS value was highest (2.74Pa) in the peak systole for the 1.5 L1/L2 of the Cx configuration, while the maximum WSS value equaled 2 Pa for all length ratios of the Bif modification (with the WSS found for L1/L2=0.3 being marginally higher). There was greater discrepancy in the WSS values for all L1/L2 ratios of the Cx bifurcation compared to Bif. Different L1/L2 rations are shown to have an impact on the pressure distribution along the entire EG while the length ratio predisposing to highest helicity or WSS values is also determined by the iliac limbs pattern of the EG. Since current custom-made EG solutions can reproduce variability in main-body/iliac limbs length ratios, further computational as well as clinical research is warranted to delineate and predict the hemodynamic and clinical effect of variable length ratios.


Designing Mesoporous Photonic Structures for High-Performance Passive Daytime Radiative Cooling.
Passive daytime radiative cooling (PDRC) has drawn significant attention recently for electricity-free cooling. Porous polymers are attractive for PDRC since they have excellent performance and scalability. A fundamental question remaining is how PDRC performance depends on pore properties (e.g., radius, porosity), which is critical to guiding future structure designs. In this work, optical simulations are carried out to answer this question, and effects of pore size, porosity, and thickness are studied. We find that mixed nanopores (e.g., radii of 100 and 200 nm) have a much higher solar reflectance R̅solar (0.951) than the single-sized pores (0.811) at a thickness of 300 μm. With an Al substrate underneath, R̅solar, thermal emittance ε̅LWIR, and net cooling power Pcool reach 0.980, 0.984, and 72 W/m2, respectively, under a semihumid atmospheric condition. These simulation results provide a guide for designing high-performance porous coating for PDRC applications.


Leveraging Real-World Data for EMA Qualification of a Model-Based Biomarker Tool to Optimize Type-1 Diabetes Prevention Studies.
The development of therapies to prevent or delay the onset of type 1 diabetes (T1D) remains challenging, and there is a lack of qualified biomarkers to identify individuals at risk of developing T1D or to quantify the time-varying risk of conversion to a diagnosis of T1D. To address this drug development need, the T1D Consortium (i) acquired, remapped, integrated, and curated existing patient-level data from relevant observational studies, and (ii) used a model-based approach to evaluate the utility of islet autoantibodies (AAs) against insulin/proinsulin autoantibody, GAD65, IA-2, and ZnT8 as biomarkers to enrich subjects for T1D prevention. The aggregated dataset was used to construct an accelerated failure time model for predicting T1D diagnosis. The model quantifies presence of islet AA permutations as statistically significant predictors of the time-varying probability of conversion to a diagnosis of T1D. Additional sources of variability that greatly improved the accuracy of quantifying the time-varying probability of conversion to a T1D diagnosis included baseline age, sex, blood glucose measurements from the 120-minute timepoints of oral glucose tolerance tests, and hemoglobin A1c. The developed models represented the underlying evidence to qualify islet AAs as enrichment biomarkers through the qualification of novel methodologies for drug development pathway at the European Medicines Agency (EMA). Additionally, the models are intended as the foundation of a fully functioning end-user tool that will allow sponsors to optimize enrichment criteria for clinical trials in T1D prevention studies.


Textured Manganite Films Anywhere.
New paradigms are required in microelectronics when the transistor is in its downscaling limit and integration of materials presenting functional properties not available in classical silicon is one of the promising alternatives. Here, we demonstrate the possibility to grow La0.67Sr0.33MnO3 (LSMO) functional materials on amorphous substrates with properties close to films grown on single-crystalline substrates using a two-dimensional seed layer. X-ray diffraction and electron backscatter diffraction mapping demonstrate that the Ca2Nb3O10- nanosheet (NS) layer induces epitaxial stabilization of LSMO films with a strong out-of-plane (001) texture, whereas the growth of LSMO films on uncoated glass substrates exhibits a nontextured polycrystalline phase. The magnetic properties of LSMO films deposited on NS are similar to those of the LSMO grown on SrTiO3 single-crystal substrates in the same conditions (which is used as a reference in this work). Moreover, transport measurements take advantages of the texture and polycrystalline properties to induce low-field magnetoresistance at low temperature and also a high value of 40% magnetoresistance from 10 to 300 K, making it interesting for sensor applications. Therefore, the NS seed layer offers new perspectives for the integration of functional materials grown at moderate temperatures on any substrate, which will be the key for the development of oxitronics.


Treatment initiation or switch to BIC/FTC/TAF - real-world safety and efficacy data from two HIV centers in Romania.
Development of highly active antiretroviral therapy marked an important step forward in the management of people living with HIV and fixed dose combinations are now available to be used as modern antiretroviral regimens. The single-tablet regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) was recently approved in Europe and included in international guidelines and recommendations. It became available in Romania in early 2021. We present the real-world results from a retrospective analysis of patients initiating BIC/FTC/TAF in two HIV centers in Romania. This retrospective analysis included patients treated with BIC/FTC/TAF (first-line or switch) in two HIV centers in Romania, one in Bucharest and one in Iași. We collected data on baseline patient characteristics, reasons for initiation of BIC/FTC/TAF and preliminary clinical and laboratory efficacy, safety and tolerability data. All assessments had been performed according to local practice. Statistical analyses were mostly descriptive and association analysis was performed to assess changes in laboratory parameters from baseline to data cut-off (October 2021). In total, 122 patients were initiated on BIC/FTC/TAF in routine clinical practice from February to October 2021 in the two HIV centers, either as first-line or switch. The majority of patients were male (71%). The median age at baseline was 35.0 years (IQR 32.0-50.8 years). Overall, 91 patients (75%) were treatment-experienced and the most frequent reason for switch was treatment simplification (79%). The mean ± standard deviation follow-up duration on treatment with BIC/FTC/TAF was 101.6 ± 64.2 days until the cut-off date for this analysis. We found no significant changes in lipid values, blood glucose or liver enzymes, coupled with a significant decrease in viral load (p=0.001). A low number of adverse events occurred during the treatment period (n=4): two cases of fatigue and two gastrointestinal reactions. No patient discontinued BIC/FTC/TAF and the overall tolerability was good. The insights of the first report on BIC/FTC/TAF use in routine clinical practice in Romania provide an overview of effectiveness and safety to local clinicians treating this patient population.


1D kinetic modelling of the JET SOL with tungsten divertor plates.
In this work a fully kinetic model of the JET SOL with tungsten divertor plates has been developed. It includes the dynamics of main-ions (D+) and electrons, the neutrals (D, C, W) and the impurity particles (C+m, W+n). Our simulations show extremely low concentration of W impurity. We identify two reasons which are responsible for this effect: (1) for low temperature divertor plasma the energy of most of the main-ions and the impurities in a low-ionization state impinging the divertor plates is below the W-sputtering threshold energy; (2) with increasing temperature the W-sputtering increases, but the potential drop across the divertor plasma increases too, so that most of the W ions are reabsorbed at the divertors.


Molecular networks in melanoma invasion and metastasis.
Metastatic melanoma accounts for approximately 80% of skin cancer-related deaths. Up to now there has been no effective treatment for stage IV melanoma patients due to the complexity and dissemination potential of this disease. Melanomas are heterogeneous tumors in which conventional therapies fail to improve overall survival. Targeted therapies are being developed, but the final outcome can be hampered by the incomplete knowledge of the process of melanoma progression. Even if the intracellular pathways are similar, the interaction of the cells with the surrounding environment should be taken into consideration. This article seeks to highlight some of the advances in the understanding of the molecular mechanisms underlying melanoma dissemination.


Surgically-assisted rapid maxillary expansion (SARME): indications, planning and treatment of severe maxillary deficiency in an adult patient.
Maxillary deficiency, also called transverse deficiency of the maxilla, may be associated with posterior crossbite, as well as with other functional changes, particularly respiratory. In adult patients, because of bone maturation and the midpalatal suture fusion, rapid maxillary expansion has to be combined with a previous surgical procedure to release the areas of resistance of the maxilla. This procedure is known as surgically-assisted rapid maxillary expansion (SARME). This study discusses the indications, characteristics and effects of SARME, and presents a clinical case of transverse and sagittal skeletal maxillary discrepancy treated using SARME and orthodontic camouflage.


Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition.
Influenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and the economy. Therefore, a large effort has been devoted to the development of new anti-influenza virus drugs directed to viral targets, as well as to the identification of cellular targets amenable to anti-influenza virus therapy. Here we have addressed the identification of such potential cellular targets by screening collections of drugs approved for human use. We reasoned that screening with a green fluorescent protein-based recombinant replicon system would identify cellular targets involved in virus transcription/replication and/or gene expression and hence address an early stage of virus infection. By using such a strategy, we identified Montelukast (MK) as an inhibitor of virus multiplication. MK inhibited virus gene expression but did not alter viral RNA synthesis in vitro or viral RNA accumulation in vivo The low selectivity index of MK prevented its use as an antiviral, but it was sufficient to identify a new cellular pathway suitable for anti-influenza virus intervention. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated with MK or left untreated, we showed that it stimulates the PERK-mediated unfolded protein stress response. The phosphorylation of PERK was partly inhibited in virus-infected cells but stimulated in MK-treated cells. Accordingly, pharmacological inhibition of PERK phosphorylation led to increased viral gene expression, while inhibition of PERK phosphatase reduced viral protein synthesis. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection. Influenza A viruses are responsible for annual epidemics and occasional pandemics with important consequences for human health and the economy. The unfolded protein response is a defense mechanism fired by cells when the demand of protein synthesis and folding is excessive, for instance, during an acute virus infection. In this report, we show that influenza virus downregulates the unfolded protein response mediated by the PERK sensor, while Montelukast, a drug used to treat asthma in humans, specifically stimulated this response and downregulated viral protein synthesis and multiplication. Accordingly, we show that PERK phosphorylation was reduced in virus-infected cells and increased in cells treated with Montelukast. Hence, our studies suggest that modulation of the PERK-mediated unfolded protein response is a target for influenza virus inhibition.


A Pathophysiology of Type 2 Diabetes Unrelated to Metabolic Syndrome.
Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we re-evaluated this hypothesis. We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3 to 9 of the Whitehall II study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the National Cholesterol Education Program Adult Treatment Panel III score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, high-density lipoprotein cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.


The role of competition in word learning via referent selection.
Previous research suggests that competition among the objects present during referent selection influences young children's ability to learn words in fast mapping tasks. The present study systematically explored this issue with 30-month-old children. Children first received referent selection trials with a target object and either two, three or four competitor objects. Then, after a short delay, children were tested on their ability to retain the newly fast-mapped names. Overall, the number of competitors did not affect children's ability to form the initial name-object mappings. However, only children who encountered few competitors during referent selection demonstrated significant levels of retention. Results and implications are discussed in terms of the role of competition in studies of children's fast mapping. The relationship between referent selection and full word learning is also discussed.


Techniques to measure pilus retraction forces.
The importance of physical forces in biology is becoming more appreciated. Neisseria gonorrhoeaehas become a paradigm for the study of physical forces in the bacterial world. Cycles of elongations and retractions of Type IV pili enables N. gonorrhoeaebacteria to exert forces on its environment, forces that play major roles in the life cycle of this pathogen. In order to better understand the role of these forces, there is a need to fully characterize them. Here, we present two different techniques, optical tweezers and Polyacrylamide MicroPillars (PoMPs), for measuring pilus retraction forces. Initially designed for N. gonorrhoeae, these assays can be readily modified to study other pilus-bearing bacteria including Neisseria meningitidis.


Photosynthetic Carbon Metabolism in Leaves and Isolated Chloroplasts from Spinach Plants Grown under Short and Intermediate Photosynthetic Periods.
Responses of foliar and isolated intact chloroplast photosynthetic carbon metabolism observed in spinach (Spinacia oleracea cv Wisconsin Bloomsdale) plants exposed to a shortened photosynthetic period (7-hour light/17-hour dark cycle), were used as probes to examine in vivo metabolic factors that exerted rate determination on photosynthesis (PS) and on starch synthesis. Compared with control plants propagated continuously on a 12-hour light/12-hour dark cycle, 14 to 15 days were required, subsequent to a shift from 12 to 7 hours daylength, for 7-hour plants to begin to grow at rates comparable to those of 12-hour daylength plants. Because of shorter daily durations of PS, daily demand for photosynthate by growth processes appeared to be greater in the 7-hour than in the 12-hour plants. The result was that 7-hour plants established a 1.5- to 2.0-fold higher total PS rate than 12-hour plants.Intact chloroplasts isolated from the leaves of 7-hour plants (7-h PLD) displayed 1.5- to 2.0-fold higher PS rates than plastids isolated from 12-hour plants (12-h PLD). Plastid lamellae prepared from 7- and 12-h PLD isolates displayed equivalent rates of ferredoxin-dependent ATP and NADPH photoformation indicating that electron transport processes were not factors in the establishment of higher 7-h PLD PS rates. Analyses, both in leaves as well as intact PLD isolates, of dark to light transitional increases in Calvin cycle intermediates, e.g., ribulose-1,5-bisphosphate (RuBP) and 3-phosphoglycerate (3-PGA), as well as estimations of activities of RuBP carboxylase and fructose-1,6-bisphosphate phosphatase, indicated that 7-hour plant leaves displayed higher PS rates (than 12-hour plants), because there was a higher magnitude of activity of the Calvin cycle.Although both the foliar level of starch and sucrose, as well as starch synthesis rate, often was higher in 7-hour compared with 12-hour plant foliage, the higher 7-hour plant total PS rates indicated that maximal sucrose and starch levels did not mediate any ;feedback' inhibition of PS. The higher 7-hour plant foliar and PLD PS rates resulted in higher glucose-1-P levels as well as a higher ratio of 3-PGA:Pi, both factors of which would enhance the activity of chloroplast ADP-glucose pyrophosphorylase, and which were attributed to be causal to the higher starch synthesis rates observed in 7-hour plant foliage and PLD isolates.


[A case of renal cell carcinoma presenting as spontaneous renal rupture].
A case of renal carcinoma presenting as spontaneous renal rupture is reported. A 50-year-old man was admitted to our hospital with the chief complaint of left lumbal pain. There was no evidence of recent trauma. Intravenous pyelography showed extravasation of perirenal area and space-occupying lesion at the left upper pole of the kidney. Left perirenal hemorrhage was found on computed tomography (CT scan). Suspecting extracapsular hemorrhage caused by rupture of the renal tumor, we performed nephrectomy. Histological diagnosis was renal cell carcinoma, alveolar type, clear cell subtype, grade 2, INF alpha, pT2. The patient has been well without local recurrence or distant metastasis for 9 months after the operation. To our knowledge, this is the 16th case or renal cell carcinoma with spontaneous rupture, reported in the Japanese literature, and the 7th case of extracapsular renal rupture.


Implementation of a multidisciplinary ventilator-weaning and sedation protocol in a community intensive care unit.
Prolongation of mechanical ventilation poses serious personal and financial threats to healthcare consumers. To that end, many healthcare-related groups have established mechanisms for rapid weaning and subsequent extubation of mechanically ventilated patients. Our objectives were to create and implement an evidenced-based, multidisciplinary care-driven ventilator-weaning protocol as well as revise existing ventilator sedation protocols to decrease length of stay in addition to time spent on the ventilator. Our findings are presented in this article.


A Search for Secondary Hypertension: "Where's Waldo?"
Hypertension is an important modifiable risk factor for cardiovascular disease and stroke. Most cases are diagnosed as essential hypertension however, in some patients, a secondary (and potentially curable) cause is identified. Selecting the right patient to screen for a secondary cause can be challenging and certain clinical and laboratory characteristics can guide work-up. We report a case of a 67-year-old man who presented with intracranial hemorrhage. He had a history of resistant hypertension for three decades and chronic hypokalemia while on a non-diuretic antihypertensive regimen. We discuss our approach to a hypertensive hypokalemic phenotype that led to the diagnosis of Liddle's syndrome with complete amelioration of hypokalemia with directed therapy. This case highlights the importance of accurate and early screening for causes of secondary hypertension in the outpatient community, and in doing so, preventing downstream catastrophic outcomes. It is imperative to develop a clear, concise approach to secondary hypertension, and raising awareness for the importance of early diagnosis as it can potentially avoid downstream sequela.


Provision of pharmacy services in community health centers and migrant health centers.
To assess the frequency with which pharmacy services are provided in community health centers (CHCs) and migrant health centers (MHCs), the importance of these services in these settings, and pharmacists' preparedness to provide these services and to determine whether pharmacist- and site-specific characteristics are related to the provision of pharmacy services. A self-administered mail survey was used to collect information on the provision of traditional pharmacy services and on the provision of pharmaceutical care services in four domains: collecting, organizing, and evaluating information; formulating a course of action; providing medications and counseling patients; and monitoring and managing patient outcomes. Data were also gathered on pharmacist- and site-specific characteristics. Descriptive and inferential statistics were calculated. Surveys were mailed to a sample of 1,260 contact persons (medical/executive directors and pharmacists). Pharmacist-reported frequency of the provision of pharmacy services, respondents' perceptions regarding the importance of the provision of pharmacy services, and respondents' perceived level of preparedness to provide pharmacy services. Pharmacists in CHCs and MHCs provided traditional services very often, felt that the services were important, and felt very prepared to provide the services. Although frequency and perceived importance and preparedness varied across and within the four pharmaceutical care domains, pharmacists most often reported collecting, organizing, and evaluating information and providing medications and counseling patients. Least often reported was formulating a course of action, followed by monitoring and managing patient outcomes. Similarly, pharmacists felt least prepared to provide these services. Pharmacists who had received additional education and training reported that they provided pharmacy services significantly more often (P < .05) and felt significantly more prepared to provide the services. Additional pharmacy-related education and training may be helpful in preparing pharmacists in CHCs and MHCs to increase their provision of pharmaceutical care services.


Describing patients with a duration of sick leave over and under one year in Norway.
This study aimed to describe the somatic, social, psychological, and work-related factors that characterize participants with a duration of sick leave over and under one year. During 2012, 181 patients on long-term sick leave were consecutively recruited and asked to answer an extensive survey. Several outcomes were reported, addressing work-related factors and somatic, psychological, and social symptoms. In cross-sectional analyses, sick leave duration was dichotomized as > or < one year, based on Norwegian legislation. Linear and logistic regressions were used to estimate population probabilities and means. The estimated prevalence of pain, fatigue, anxiety, and depression was overall high. There was a tendency towards a higher prevalence of fatigue, anxiety, and depression in those with sick leave duration less than one year, with the exception of sleep problems, which was more frequent in the population with longer duration. Relationship with friends, family, co-workers, and the last workplace were worse in the population with longer duration. Cross-sectional analyses indicated that social and work-related problems are more adverse in patients with longer duration of sick leave, while psychological and somatic symptoms appear less adverse. This is one of the first studies quantitatively demonstrating these differences through comprehensive, simultaneously measured self-report questionnaires.


Regulation of FlbD activity by flagellum assembly is accomplished through direct interaction with the trans-acting factor, FliX.
The temporal and spatial transcription of late flagellar genes in Caulobacter crescentus is regulated by the sigma54 transcriptional activator, FlbD. One requirement for FlbD activity is the assembly of a structure encoded by early, class II flagellar genes. In this report, we show that the trans-acting factor FliX predominantly functions as a negative regulator of FlbD activity in the absence of the class II-encoded flagellar structure. In contrast, a mutant FliX that bypasses the transcriptional requirement for early flagellar assembly is incapable of repressing FlbD in a class II flagellar mutant. Expression of this mutant allele, fliX1, does not alter the temporal pattern of FlbD-dependent transcription. Remarkably, this mutation confers the correct cell cycle timing of hook operon transcription in a strain that cannot assemble the flagellum, indicating that the progression of flagellar assembly is a minor influence on temporal gene expression. Using a two-hybrid assay, we present evidence that FliX regulates FlbD through a direct interaction, a novel mechanism for this class of sigma54 transcriptional activator. Furthermore, increasing the cellular levels of FliX results in an increase in the concentration of FlbD, and a corresponding increase in FlbD-activated transcription, suggesting that FliX and FlbD form a stable complex in Caulobacter. FliX and FlbD homologues are present in several polar-flagellated bacteria, indicating that these proteins constitute an evolutionarily conserved regulatory pair in organisms where flagellar biogenesis is likely to be under control of the cell division cycle.


Myocardial T1 mapping and extracellular volume quantification as novel biomarkers in risk stratification of patients with systemic sclerosis.
To study the prognostic value of myocardial native T1 and extracellular volume (ECV), measured by cardiovascular magnetic resonance (CMR), in patients with systemic sclerosis (SSc). Thirty-three SSc patients (16/33 male, 48.5%) were studied using multiparametric CMR including native T1 mapping with ECV calculation, T2 mapping, and late gadolinium enhancement (LGE). Patients were followed-up for cardiac death, haemodynamically significant arrhythmia, or heart failure. Results were compared with 33 age- and gender-matched healthy controls. When compared with controls, SSc patients had higher myocardial native T1 (1,058.9±71 versus 989.4±21.4 ms, p<0.001), higher T2 (54.9±5.7 versus 50±2.5 ms, p<0.001), and ECV values (27.9±5.4% versus 24.8±2%, p<0.004). LGE was present in eight patients (24%), two subendocardial, five midwall, and four subepicardial. LGE, native T1, and ECV were significantly associated with adverse events during follow-up in multivariate Cox regression analysis. Kaplan-Meier analysis demonstrated significant divergence of the survival curves based on the presence of elevated native T1 (≥1,069 ms) or ECV (≥31.4%) values. Cardiac involvement is frequent in SSc. Both native T1 mapping and ECV represent novel non-invasive markers of myocardial fibrosis and could be used in the risk stratification of patients with SSc. CMR mapping may provide a novel biomarker for disease monitoring and study of therapies aiming to reduce myocardial fibrosis in SSc.


Bowel Oedema Necessitating Urgent Abdominal Decompression Following Cardiopulmonary Bypass: An Exaggerated Presentation of a Recognised Complication.
Gastrointestinal complications after the termination of cardiopulmonary bypass are uncommon; however, they can lead to serious consequences. We encountered an unusual case of an 11-month-old infant who developed gross abdominal distention, leading to ventilatory and haemodynamic embarrassment following separation from the cardiopulmonary bypass. This presumably was a severe manifestation of the inflammatory response observed with extracorporeal circulation, which manifested as bowel oedema and was diagnosed using point-of-care ultrasound. As a rescue measure, urgent abdominal decompression was performed by cutting open the abdominal wall, which restored the ventilator and haemodynamic parameters to almost normal values.


Cryoprecipitate prepared from plasma frozen within 24 hours after phlebotomy contains acceptable levels of fibrinogen and VIIIC.
As blood centers prepare fewer plasma products from female donors to avoid HLA antibodies, the standard starting material for cryoprecipitate (cryo), fresh-frozen plasma (FFP), might become increasingly scarce. A unit of cryo must contain at a minimum 80 IU of VIIIC and 150 mg of fibrinogen. Plasma frozen within 24 hours after phlebotomy (FP24) contains nearly equivalent levels of clotting factors as FFP at the time of thawing and, although not AABB/FDA approved for this purpose, might be a suitable starting material for cryo (cryo24) manufacture. FP24 was collected from 20 male donors and cryo24 was subsequently prepared according to standard blood center protocols. The cryo24 was then thawed and VIIIC, von Willebrand factor (VWF) antigen, and fibrinogen levels were measured in these cryo24 units and compared to the corresponding levels in 20 randomly selected units of standard cryo (prepared from FFP). The mean (+/-SD) levels in cryo and cryo24 at the time of thawing were as follows: fibrinogen (mg/unit) 455.8 (+/-172.6) and 575.8 (+/-185.9; p = 0.04), VIIIC (IU/unit) 216.1 (+/-52.3) and 252.4 (+/-70.1; p = 0.07), and VWF (IU/unit) 448.1 (+/-118.9) and 505.9 (+/-135.1; p = 0.16), respectively. All units of standard cryo and cryo24 met the current minimum content standards. All units of cryo24 in this pilot study met the current minimum content standards for cryo. While clinical studies of its efficacy are warranted, cryo24's in vitro characteristics are at least equivalent to that of standard cryo.