Diurnal expression of functional and clock-related genes throughout the rat HPA axis: system-wide shifts in response to a restricted feeding schedule.
The diurnal rhythm of glucocorticoid secretion depends on the suprachiasmatic (SCN) and dorsomedial (putative food-entrainable oscillator; FEO) nuclei of the hypothalamus, two brain regions critical for coordination of physiological responses to photoperiod and feeding cues, respectively. In both cases, time keeping relies upon diurnal oscillations in clock gene (per1, per2, and bmal) expression. Glucocorticoids may play a key role in synchronization of the rest of the body to photoperiod and food availability. Thus glucocorticoid secretion may be both a target and an important effector of SCN and FEO output. Remarkably little, however, is known about the functional diurnal rhythms of the individual components of the hypothalamic-pituitary-adrenal (HPA) axis. We examined the 24-h pattern of hormonal secretion (ACTH and corticosterone), functional gene expression (c-fos, crh, pomc, star), and clock gene expression (per1, per2 and bmal) in each compartment of the HPA axis under a 12:12-h light-dark cycle and compared with relevant SCN gene expression. We found that each anatomic component of the HPA axis has a unique circadian signature of functional and clock gene expression. We then tested the susceptibility of these measures to nonphotic entrainment cues by restricting food availability to only a portion of the light phase of a 12:12-h light-dark cycle. Restricted feeding is a strong zeitgeber that can dramatically alter functional and clock gene expression at all levels of the HPA axis, despite ongoing photoperiod cues and only minor changes in SCN clock gene expression. Thus the HPA axis may be an important mediator of the body entrainment to the FEO.


The effect of in vivo endotoxin on myocardial function in vitro.
Isolated perfused working hearts from male adult Sprague Dawley rats were used to examine myocardial performance following acute in vivo endotoxin administration (LD50-6-hour). Three hours after endotoxin administration, cardiac output and peak systolic pressure in the isolated perfused working heart were depressed 25-50% over a range of left atrial filling pressures (preload) from 10 to 30 cm of water. Linear regression analysis of the relationship between myocardial work indices, oxygen uptake, and glucose oxidation indicated that the hearts from the endotoxin-treated animals required more oxygen and glucose to perform the same amount of work. Levels of cyclic 3'5' adenosine monophosphate were 72% higher in ventricular tissue from the endotoxin-treated group compared to the hearts of controls. Isoproterenol (10(-9) mol/min) raised levels of the nucleotide to the same final concentration in both groups of hearts, whereas myocardial pressure work in hearts from endotoxin-treated rats was only 70% that of control. Provision of isoproterenol, while increasing mechanical work by the hearts in the endotoxin-treated group, did not induce an increase to the same performance levels as that of control hearts not treated with isoproterenol. These data are consistent with the concept that endotoxemia produces an intrinsic defect in myocardial mechanical performance.


Direct immunological determination of aspartate aminotransferase isoenzymes.
We examined the suitability of a rapid immunological technique to determine the amount of aspartate aminotransferase (EC 22.214.171.124) isoenzymes in human serum or tissue extracts. Purified isoenzymes were absorbed as a monolayer to the surface of an indium metal film on glass. The enzyme retains immunological reactivity, allowing the specific binding of aspartate aminotransferase antibodies at the surface. The amount of isoenzyme in a specimen is estimated from the competition for the antibody between the free isoenzyme in the specimen and that at the surface. The surface is further incubated with goat antibodies to rabbit IgG, and the extent of antibody binding is determined by densitometry. There is no cross reactivity between the cytoplasmic and mitochondrial forms, so these two isoenzymes can be determined simultaneously. The minimum detectable concentration by this technique is about 50 micrograms of enzyme protein per liter. The within-day coefficient of variation for determination of either isoenzyme was about 20%. Our results suggest that normal and patients' sera contain considerably more immunologically active than catalytically active isoenzymes.


The child welfare practitioner as university teacher.
A growing number of child welfare practitioners are employed as part-time university teachers in social work programs. Understanding and utilizing practice ideas, methods, and skills applicable to the teaching role can facilitate the transition from agency to classroom.


Snoring: not funny--not hopeless.
Snoring means obstructive breathing during sleep, and its most exaggerated form is obstructive sleep apnea. Mild snoring may respond to simple self-help remedies. Heavy snoring responds well to the surgical removal or reconstruction of obstructive elements in the hypopharynx, nasopharynx or nasal passages.


Tryptase inhibits motility of human spermatozoa mainly by activation of the mitogen-activated protein kinase pathway.
We previously localized protease-activated receptor 2 (PAR-2) on human spermatozoa and demonstrated that activation of PAR-2 by the mast cell (MC) product tryptase inhibits sperm motility. Importantly, tryptase-secreting MCs are encountered in the male and female genital tract, implying that MC-spermatozoa interactions may be as yet unrecognized factors affecting sperm fertilizing ability. In order to elucidate how tryptase via activation of PAR-2 acts in human spermatozoa, we studied intracellular signal transduction events. Impairment of sperm motility by tryptase was not dependent on the presence of extracellular Ca2+ and tryptase did not alter intracellular Ca2+ levels. Pre-incubation with pertussis toxin (PTX) failed to prevent tryptase effects on sperm motility. Western blot analyses revealed that tryptase increased phosphorylation of the mitogen-activated protein kinases (MAPK) ERK1/2, an effect which was blocked by the MAPK pathway inhibitor PD98059. Pre-treatment of spermatozoa with this inhibitor also blocked the inhibtion of sperm motility evoked by tryptase. These results indicate that tryptase acts via the ERK1/2 pathway to inhibit motility of human spermatozoa.


[Vitamin D levels among Chilean older subjects with low energy hip fracture].
Vitamin D deficiency is a common condition affecting 40-100% of geriatric population. To determine the prevalence of vitamin D insufficiency and deficiency in geriatric population surgically treated for hip fracture. Analysis of a database of patients aged over 60 years operated for a low energy hip fracture in a three years period. Vitamin D was measured in identified patients, using a blood sample obtained on admission to the hospital. A logistic regression was carried out to evaluate age, gender, morbidity index and season as predictors of vitamin D deficiency. Two hundred and twenty-eight patients aged 84 ± 7 years (82% females), were included in the analysis. One hundred eighty-three patients (80%) presented vitamin D levels below 20 ng/dl (deficiency) and 39 patients (18%) presented with levels between 20 and 30 ng/dl (insufficiency), totaling 98% of patients with hypovitaminosis D. Vitamin D deficiency was especially common among patients with higher American Society of Anesthesiologists (ASA) Physical Status Classification System and during winter-spring period. A negative correlation between age and the proportion of subjects with vitamin D deficiency was found. There was no relation between gender and vitamin D levels. Vitamin D deficiency is especially prevalent in older subjects with hip fracture, reaching 98% in the studied population.


Fate of copper in ponds.
Treatments of 3 ppm copper sulfate (CuSO4-5H2O) were applied to two small aquatic systems in Michigan in 1971. To study the pathways of the added copper, samples of water, sediment, aquatic macrophytes, filamentous algae, and fish were collected and analyzed by atomic absorption. Sampling was initiated before treatment and continued up to 4 months in one of the ponds. Dissolved copper concentrations in water decreased rapidly immediately after treatment and then gradually to background levels. Reduction of dissolved copper may have involved initial precipitation of an insoluble compound, such as malachite, followed by sediment adsorption of soluble copper complexes and copper released from aquatic plants. Levels of copper in sediment increased rapidly at first and gradually later in the study. Aquatic plants and filamentous algae accumulated very high levels of copper. Uptake rates were apparently affected by water temperature and growth stages of the plants. Data indicate that aquatic macrophytes developing in one pond 10 weeks after treatment took up copper from the sediment. Although green sunfish (Lepomis cyanellus) accumulated copper soon after treatment, levels returned to background later in the study.


Angina after aortocoronary bypass grafting: combined medical therapy including nifedipine.
A second coronary artery revascularization procedure often yields poor results. Nifedipine, a calcium antagonist, was added to the current medical therapy consisting of maximal doses of beta blockers and nitrates in a group of 18 patients who had had one revascularization procedure and subsequently had class 3 and 4 angina pectoris. The overall favorable clinical response was 72%. The average dose of nifedipine to achieve a clinical response was 90 mg/day. Left ventricular function improved with time. We believe nifedipine is an important adjunct in the management of angina after coronary bypass operation.


Advances in the treatment of Hodgkin's lymphoma.
Given the successful treatment for most patients with Hodgkin's lymphoma, efforts have been directed primarily toward improving outcomes for the minority of patients with poor prognosis or relapsed disease or reducing the late effects of therapy for long-term survivors. Recently, a simple and clinically useful prognostic scoring system was developed for patients with advanced disease. This system allows better risk assessment for individual patients and more uniformity among patients participating in clinical trials. In addition, trials using newer chemotherapeutic regimens such as Stanford V or BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are maturing with promising results. Other studies are helping to define the role of high-dose therapy for patients with Hodgkin's lymphoma, although biologic treatments such as cellular or antibody-based therapies are still in early phases of development. Lastly, positron emission tomographic scanning is emerging as a useful tool in staging and following Hodgkin's lymphoma.


Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial.
The TME trial investigated the value of preoperative short-term radiotherapy in combination with total mesorectal excision (TME). Long-term results are reported after a median follow-up of 12 years. Between Jan 12, 1996, and Dec 31, 1999, 1861 patients with resectable rectal cancer without evidence of distant disease were randomly assigned to TME preceded by 5 × 5 Gy radiotherapy or TME alone (ratio 1:1). Randomisation was based on permuted blocks of six with stratification according to centre and expected type of surgery. The primary endpoint was local recurrence, analysed for all eligible patients who underwent a macroscopically complete local resection. 10-year cumulative incidence of local recurrence was 5% in the group assigned to radiotherapy and surgery and 11% in the surgery-alone group (p<0·0001). The effect of radiotherapy became stronger as the distance from the anal verge increased. However, when patients with a positive circumferential resection margin were excluded, the relation between distance from the anal verge and the effect of radiotherapy disappeared. Patients assigned to radiotherapy had a lower overall recurrence and when operated with a negative circumferential resection margin, cancer-specific survival was higher. Overall survival did not differ between groups. For patients with TNM stage III cancer with a negative circumferential resection margin, 10-year survival was 50% in the preoperative radiotherapy group versus 40% in the surgery-alone group (p=0·032). For all eligible patients, preoperative short-term radiotherapy reduced 10-year local recurrence by more than 50% relative to surgery alone without an overall survival benefit. For patients with a negative resection margin, the effect of radiotherapy was irrespective of the distance from the anal verge and led to an improved cancer-specific survival, which was nullified by an increase in other causes of death, resulting in an equal overall survival. Nevertheless, preoperative short-term radiotherapy significantly improved 10-year survival in patients with a negative circumferential margin and TNM stage III. Future staging techniques should offer possibilities to select patient groups for which the balance between benefits and side-effects will result in sufficiently large gains. The Dutch Cancer Society, the Dutch National Health Council, and the Swedish Cancer Society.


Evaluation of rear-end crash risk at work zone using work zone traffic data.
This paper aims to evaluate the rear-end crash risk at work zone activity area and merging area, as well as analyze the impacts of contributing factors by using work zone traffic data. Here, the rear-end crash risk is referred to as the probability that a vehicle is involved in a rear-end crash accident. The deceleration rate to avoid the crash (DRAC) is used in measuring rear-end crash risk. Based on work zone traffic data in Singapore, three rear-end crash risk models are developed to examine the relationship between rear-end crash risk at activity area and its contributing factors. The fourth rear-end crash risk model is developed to examine the effects of merging behavior on crash risk at merging area. The ANOVA results show that the rear-end crash risk at work zone activity area is statistically different from lane positions. Model results indicate that rear-end crash risk at work zone activity area increases with heavy vehicle percentage and lane traffic flow rate. An interesting finding is that the lane closer to work zone is strongly associated with higher rear-end crash risk. A truck has much higher probability involving in a rear-end accident than a car. Further, the expressway work zone activity area is found to have much larger crash risk than arterial work zone activity area. The merging choice has the dominated effect on risk reduction, suggesting that encouraging vehicles to merge early may be the most effective method to reduce rear-end crash risk at work zone merging area.


Instant effects of peppermint essential oil on the physiological parameters and exercise performance.
Effect of peppermint on exercise performance was previously investigated but equivocal findings exist. This study aimed to investigate the effects of peppermint ingestion on the physiological parameters and exercise performance after 5 min and 1 h. Thirty healthy male university students were randomly divided into experimental (n=15) and control (n=15) groups. Maximum isometric grip force, vertical and long jumps, spirometric parameters, visual and audio reaction times, blood pressure, heart rate, and breath rate were recorded three times: before, five minutes, and one hour after single dose oral administration of peppermint essential oil (50 µl). Data were analyzed using repeated measures ANOVA. Our results revealed significant improvement in all of the variables after oral administration of peppermint essential oil. Experimental group compared with control group showed an incremental and a significant increase in the grip force (36.1%), standing vertical jump (7.0%), and standing long jump (6.4%). Data obtained from the experimental group after five minutes exhibited a significant increase in the forced vital capacity in first second (FVC1)(35.1%), peak inspiratory flow rate (PIF) (66.4%), and peak expiratory flow rate (PEF) (65.1%), whereas after one hour, only PIF shown a significant increase as compare with the baseline and control group. At both times, visual and audio reaction times were significantly decreased. Physiological parameters were also significantly improved after five minutes. A considerable enhancement in the grip force, spiromery, and other parameters were the important findings of this study. Conclusion : An improvement in the spirometric measurements (FVC1, PEF, and PIF) might be due to the peppermint effects on the bronchial smooth muscle tonicity with or without affecting the lung surfactant. Yet, no scientific evidence exists regarding isometric force enhancement in this novel study.


Low active loading of cargo into engineered extracellular vesicles results in inefficient miRNA mimic delivery.
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop. Computational modeling demonstrated a stable interaction between the modified pre-miR-199a loop and TAT peptide. EMSA gel shift, recombinant Dicer processing and luciferase binding assays confirmed the binding, processing and functionality of the modified pre-miR-199a. The TAT-TAR interaction enhanced the loading of the miR-199a into EVs by 65-fold. Endogenously loaded EVs were ineffective at delivering active miR-199a-3p therapeutic to recipient SK-Hep1 cells. While the low degree of miRNA loading into EVs through this approach resulted in inefficient distribution of RNA cargo into recipient cells, the TAT TAR strategy to load miRNA into EVs may be valuable in other drug delivery approaches involving miRNA mimics or other hairpin containing RNAs.


The mucinous variant of columnar cell lesions.
Mucin-producing columnar cell lesions (CCL) are a rare, new entity in the breast. The aim of this study was to describe the incidence and follow-up of mucinous CCLs. Of 4164 breast core needle biopsies (CNBs), 291 showed a CCL and 21 atypical ductal hyperplasia (ADH) originating in a CCL (ADH-CCL). Mucin production was present in 17 of 291 (5.8%) CCLs and three of 21 (14.3%) ADH-CCLs, together concerning 0.5% of all CNBs. The most common mucinous CCL pattern was a columnar cell change without atypia, and almost all were detected with microcalcifications as an abnormality at mammography. During a median follow-up of 3.1 years, no invasive carcinoma or ductal carcinoma in situ was detected. MUC2 was expressed in intraluminal mucin in 12 of 15 (80%) mucinous CCLs, and showed cytoplasmic expression in five of 15 (33%) mucinous CCLs seen in CNBs. Moreover, mucinous CCLs were significantly more common in association with 46 mucinous carcinomas than in 46 ductal carcinomas (28% versus 9%). Mucinous CCLs are rare lesions, with an incidence of about 0.5% in breast CNBs, usually presenting with microcalcifications. Although these lesions might play a role in the mucinous progression spectrum, the short-term risk of progression to more advanced lesions seems to be low.


Familial adenomatous polyposis (FAP) and gender. Does gender influence the genetic transmission of FAP?
Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with a penetrance close to 100% at the age of 40 years. The incidence is thought to be equal among both sexes, but we noticed an excess of males undergoing primary surgery for FAP at our institution. The aim of the study is to investigate the hypothesis that FAP patients produce an excess of affected male offspring. We identified all families with known APC mutation in the polyposis registry at St Mark's from its foundation until October 2009. We analysed their pedigrees with respect to gender of the affected individuals with progeny and to the gender and mutation status of their offspring. Only individuals with complete data regarding their offspring (gender and mutation status) were included. We identified 666 (324 males and 342 females) affected individuals with progeny. We analysed the progeny of 368 (182 males, 186 females) affected individuals with complete data on all offspring: 235 (27.5%) affected males, 212 (24.8%) affected females, 207 (24.3%) unaffected males and 200 (23.4%) unaffected females. The overall ratio of affected/unaffected and male/female offspring did not differ from the expected 50%. Further sub-analysis by gender of parents did not show any statistically significant difference in gender and mutation status of offspring. In addition the mean number of children per affected parent did not depend on gender (males 2.34; females 2.30). This study shows that gender does not influence the genetic transmission of FAP. The excess of males undergoing primary surgery at our institution is probably a result of referral bias.


Malignant phyllodes tumors: a review of 752 cases.
Malignant phyllodes tumor (MPT) is a rare breast malignancy. Because of the scarcity of the disease, there are no evidence-based treatment or follow-up guidelines established. This study evaluated the survival of MPT patients to create recommendations for management. We identified 752 cases of malignant phyllodes tumors in the California Cancer Registry from the years 1988 to 2003. Relative survival was determined using Berkson-Gage life table analysis which was then compared with the relative survival of nonphyllodes breast cancer patients. For MPT patients, the relative annual survival at 1 year was 94 per cent and at 10 years was 99.6 per cent. Thus, after 10 years, these patients are no more likely to die than the general population. At 10 years, the relative cumulative survival of the MPT patients was 87.4 per cent, whereas the nonphyllodes breast cancer patients had only a 57.2 per cent relative cumulative survival. MPT patients with localized disease had a higher 10-year relative cumulative survival than those with regional disease (90.9% vs. 61.5%, P < 0.001). MPT has a good prognosis, particularly in patients with localized disease. After 10 years, MPT patients have no increased mortality relative to the general population. Clinicians should plan these patients' follow-up accordingly.


Regulation of in vitro renin secretion by ANG II feedback manipulation in vivo in the ovine fetus.
The renin-angiotensin system is critically important to fetal cardiovascular function and organ development. The feedback regulation of renin secretion by ANG II develops early in gestation yet does not linearly progress from fetal life to adulthood. Renin secretion is elevated in late gestation compared with earlier or postnatal time periods, which suggests that some component of the negative feedback regulation of renin secretion is less sensitive in late gestation. We examined in fetal sheep the age-related consequence of chronic in vivo manipulation of ANG II on renal renin secretion measured in vitro. Immature (101-103 days of gestation) and mature (130-133 days of gestation) fetuses were treated for 72 h with enalaprilat, ANG II or vehicle. Content and basal and isoproterenol-stimulated secretion of prorenin (PR) and active renin (AR) from fetal kidney cortical slices were determined. Enalaprilat pretreatment in vivo increased renal renin content and basal and stimulated secretion of PR and AR in vitro even in immature animals. Immunohistochemical localization showed that enalaprilat treatment caused an age-related recruitment of renin-containing juxtaglomerular cells. Conversely, ANG II pretreatment decreased basal and stimulated PR and AR secretion from immature fetal kidneys, but only inhibited PR secretion from mature kidneys. It also caused an age-related decrease in the percentage of renin-containing juxtaglomerular cells. These results suggest that ANG II feedback modulates not only the synthesis and content of renin, but the sensitivity of the coupling between stimulus and secretion. A critical observation of our study is that the higher renal tissue concentrations of prorenin and active renin in late gestation may be a consequence of reduced sensitivity to ANG II feedback; this is consistent with the increased plasma concentrations of renin found in near-term mammals.


Latissimus dorsi transfer using bone block technique to restore active external rotation in reversed total shoulder arthroplasty.
The aim was to compare the outcome of a reversed shoulder arthroplasty with a latissiumus dorsi transfer without (LD-BB) or with bone block (LD+BB) in patients with rotator cuff-deficient shoulders and combined loss of active elevation and external rotation. Postoperative patients with LD+BB were not immobilized compared to 6 weeks of immobilization in patients with LD-BB. Clinical outcome was evaluated using the Constant Score, ADLER score and satisfaction rate. Also radiological follow-up of the bone-block was performed. In total 29 patients (21 LD+BB, 8 LD-BB) were evaluated. There was no significant difference between both groups at 3 months, 6 months and 1 year in clinical outcome. The radiological evaluation revealed remodellation and ingrowth of the bone block in all but one patient. We conclude that the bone block procedure is a safe technique to perform a LD transfer with good clinical outcome. It also allows early mobilisation and radiological evaluation.


Chemical characteristics and valuation of sewage sludge from four different wastewater treatment plants.
Sewage sludge contains plant nutrients and organic matter in its composition, making it a potential partial substitute for mineral fertilizers if it meets environmental, agronomic, and sanitary standards. The objective was to evaluate the content of nutrients and heavy metals in the sludge generated in four wastewater treatment stations (WWTPs) in Rio de Janeiro state and assess its potential value and usefulness. The samples of 19 batches from the WTTPs Alegria, Barra da Tijuca, Ilha do Governador, and Sarapuí were analyzed. The WWTPs differ in methods and processes used for treating sewage and sludge. The total contents of C, N, P, K, Ca, Mg, Fe, Al, Na, Co, Mn, As, Ba, Cd, Cr, Cu, Ni, Se, Pb, and Zn were evaluated, as well as the ratio C/N, pH, organic matter content, and electrical conductivity. The grouping of sludge samples was assessed using principal components (PCA) and cluster analysis. The economic valuation of sludge was conducted utilizing the substitute goods method, which compared the sludge's N-P-K contents with the prices of consolidated nutrient sources. All the evaluated sludge batches exhibited concentrations of heavy metals below the limits allowed by Brazilian law, along with high levels of nutrients and organic matter. Considering the chemical characteristics, all evaluated materials showed potential for agricultural use, but it is crucial to evaluate the microbiological characteristics of sludge batches before agriculture application. PCA and cluster analysis demonstrated that sludge samples from the same WWTP clustered close to each other, demonstrating higher similarity among themselves than with samples from other WWTPs. The sludge had an average added value of U$ 88.46 per megagram, considering the total contents of N, P, and K in its composition. Land application of sewage sludge can reduce the need to purchase mineral fertilizers, thereby supporting the feasibility of reusing this material in the agricultural sector.


Patch-clamp-induced perturbations of [Ca(2+)](i) activity in somatotropes.
Somatotropes and GC cells, a GH-producing cell line, exhibit [Ca(2+)](i) oscillations that result from rhythmic Ca(2+) action potentials. Determination of this operating mode required simultaneous recording of both parameters by fura-2 imaging and patch-clamp techniques. In order to test whether patch recording induces artificial alteration of the [Ca(2+)](i) oscillatory pattern, we recorded separately or simultaneously [Ca(2+)](i) and membrane potential. In the absence of any other stimulation, seal formation in patch-clamp recording evoked by itself a 2.5- to 4-fold persistent increase in basal [Ca(2+)](i), speeded up their frequency (from 0.03-0.17 to 0.4 Hz) and changed their pattern to a tonic mode. Patch-induced [Ca(2+)](i) increase was reproduced by mechanical contact between the pipette and the membrane. It was reduced by nifedipine, a blocker of L-type Ca(2+) channels, as well as by removal of external Na(+). It was fully blocked by external Ca(2+) removal or gadolinium. All patch-clamp-induced perturbations were reversed by membrane hyperpolarization. We propose that patch-clamp recording evokes Ca(2+) entry through L-type Ca(2+) channels either directly, or indirectly via membrane depolarization. This shows that patch recordings in endocrine cells showing mechanosensitivity have to be interpreted with caution, and explains why long-lasting patch recordings are so difficult to obtain.


[Florence Nightingale: an Italian portrait.].
Florence Nightingale was the pioneer of modern nursing. The aim of this article is to give a brief review of her character. Her Christian name derives from her birthplace, albeit her English nationality. She was trained in England, save for a brief spell in Germany. The nursing profession of her time left much to desire; competent nurses were hard to find, their preparation was poor, and so was availability. In Paris, she first encountered real issues related to nursing and sanitation, but did not tarry a moment to get to grips with them. She did not hide her organisational skills and humanitarian outlook, and the occasion to put them to good use presented itself with the Crimean War, where the opposition of army officers only aggravated the arduous process of putting local hygienic conditions under control. Invariably, Florence Nightingale was perceived by soldiers as an almost mythical mother figure, gentle and authoritative, a single firm point in moments of physical or moral decline. She did her best to help improve conditions in India, despite the odds. She died in London in 1910.


Is there an association between the individual anatomy of the scapula and the development of rotator cuff tears or osteoarthritis of the glenohumeral joint?: A radiological study of the critical shoulder angle.
We hypothesised that a large acromial cover with an upwardly tilted glenoid fossa would be associated with degenerative rotator cuff tears (RCTs), and conversely, that a short acromion with an inferiorly inclined glenoid would be associated with glenohumeral osteoarthritis (OA). This hypothesis was tested using a new radiological parameter, the critical shoulder angle (CSA), which combines the measurements of inclination of the glenoid and the lateral extension of the acromion (the acromion index). The CSA was measured on standardised radiographs of three groups: 1) a control group of 94 asymptomatic shoulders with normal rotator cuffs and no OA; 2) a group of 102 shoulders with MRI-documented full-thickness RCTs without OA; and 3) a group of 102 shoulders with primary OA and no RCTs noted during total shoulder replacement. The mean CSA was 33.1° (26.8° to 38.6°) in the control group, 38.0° (29.5° to 43.5°) in the RCT group and 28.1° (18.6° to 35.8°) in the OA group. Of patients with a CSA > 35°, 84% were in the RCT group and of those with a CSA < 30°, 93% were in the OA group. We therefore concluded that primary glenohumeral OA is associated with significantly smaller degenerative RCTs with significantly larger CSAs than asymptomatic shoulders without these pathologies. These findings suggest that individual quantitative anatomy may imply biomechanics that are likely to induce specific types of degenerative joint disorders.


Efficient end-group functionalization and diblock copolymer synthesis via Au(III) polymer reagents.
Herein, we describe the synthesis of bench-stable organometallic Au(III) terminated polymer reagents. These reagents mediate the chemoselective S-arylation of thiol-containing small molecules and polymers to yield functionalized mono-telechelic polymers and diblock copolymers, respectively. These transformations proceed rapidly within minutes and produce conjugates in quantitative conversion, making this strategy a robust addition to the polymer functionalization toolbox.


The multifunctional protein glyceraldehyde-3-phosphate dehydrogenase is both regulated and controls colony-stimulating factor-1 messenger RNA stability in ovarian cancer.
Although glyceraldehyde-3-phosphate dehydrogenase's (GAPDH) predilection for AU-rich elements has long been known, the expected connection between GAPDH and control of mRNA stability has never been made. Recently, we described GAPDH binding the AU-rich terminal 144 nt of the colony-stimulating factor-1 (CSF-1) 3' untranslated region (UTR), which we showed to be an mRNA decay element in ovarian cancer cells. CSF-1 is strongly correlated with the poor prognosis of patients with ovarian cancer. We investigated the functional significance of GAPDH's association with CSF-1 mRNA and found that GAPDH small interfering RNA reduces both CSF-1 mRNA and protein levels by destabilizing CSF-1 mRNA. CSF-1 mRNA half-lives were decreased by 50% in the presence of GAPDH small interfering RNA. RNA footprinting analysis of the 144 nt CSF-1 sequence revealed that GAPDH associates with a large AU-rich-containing region. The effects of binding of GAPDH protein or ovarian extracts to mutations of the AU-rich regions within the footprint were consistent with this finding. In a tissue array containing 256 ovarian and fallopian tube cancer specimens, we found that GAPDH was regulated in these cancers, with almost 50% of specimens having no GAPDH staining. Furthermore, we found that low GAPDH staining was associated with a low CSF-1 score (P = 0.008). In summary, GAPDH, a multifunctional protein, now adds regulation of mRNA stability to its repertoire. We are the first to evaluate the clinical role of GAPDH protein in cancer. In ovarian cancers, we show that GAPDH expression is regulated, and we now recognize that one of the many functions of GAPDH is to promote mRNA stability of CSF-1, an important cytokine in tumor progression.


The hyphal wall of Mucor mucedo. 1. Polyanionic polymers.
Treatment of isolated hyphal walls of Mucor mucedo with nitrous acid resulted in the release of two water-soluble polyanions: (a) a glycuronan, containing all the neutral sugars and uronic acid present in the hyphal wall and (b) an inorganic polyphosphate. The glycuronan could also be extracted quantitatively with salt solutions of high ionic strength and partially with a solution of potassium hydroxide. This is presented as evidence that the glycuronan is a genuine constituent of the cell wall, non-covalently bound to glucosamine-containing polymers which are susceptible to depolymerization by nitrous acid. By treatment with acid the glycuronan was partly converted to crystalline poly(glucuronic acid) with the properties of mucoric acid. This strongly suggests that mucoric acid, which can be extracted from the walls of M. mucedo by alkali after acid treatment, is not a genuine wall component but arises by partial acid hydrolysis of the heteropolymeric glycuronan.


Related Factor Analysis and Nursing Strategies of Diarrhea in Critically Ill Patients with Enteral Nutrition.
To explore the related factors of diarrhea in critically ill patients with enteral nutrition (EN) in the intensive care unit (ICU). This single-center retrospective study analyzed the occurrence of intolerant diarrhea in ICU patients receiving EN treatment in our hospital. By collecting clinical data, univariate and multivariate logistic regression analysis was used to screen the risk factors for diarrhea. Among 120 patients included in the study, 68 (48.33%) had diarrhea. Age (OR = 2.599, P = 0.027), use of antibiotics (OR = 3.496, P = 0.007), ICU hospitalization time (OR = 1.311, P = 0.001), and mechanical ventilation time (OR = 1.273, P = 0.035) were all independent risk factors for diarrhea in EN. Older age, frequent use of antibiotics, long ICU stay, and mechanical ventilation time can lead to diarrhea in ICU patients receiving EN treatment. It is necessary to effectively analyze the above independent factors and implement targeted interventions to improve the incidence of diarrhea in patients.


Adherence to AAP guidelines for well-child care under managed care. American Academy of Pediatrics.
To determine adherence to American Academy of Pediatrics (AAP) Recommendations for Preventive Pediatric Health Care in Monroe County, New York by individual patients and individual pediatricians under managed care practice and to compare adherence-to-recommendations rates for privately insured and publicly funded managed care patients. Using claims data for children 0 through 18 years of age cared for by pediatricians, we compared adherence to well-child care (WCC) visit recommendations for 130 572 children enrolled in a privately insured managed care system during 1992, 1993, and 1994 to 17 586 children insured by a publicly funded, Medicaid-managed care system during 1994 and 1995. Criteria for WCC visit adherence were based on 1991 AAP guidelines of 19 office visits from birth through 18 years of age. Adherence-to-recommendations rates by individual pediatricians also were determined. Despite complete financial coverage of WCC visits (with no co-payment or deductible charges) by both insurance systems, strict adherence to AAP guidelines for WCC visits was low. Only 46% of privately insured and 35% of publicly funded children received all the recommended visits during the study period. During the same period, 17% of privately insured and 35% of publicly funded managed care patients received no WCC. There was little difference in the rate of full WCC visit adherence by age in either system with the rates ranging in privately insured patients from 49% in infants (<2 years of age) to 47% in adolescents (12 through 18 years of age) and ranging in publicly funded patients from 36% to 34% in these two age groups, respectively. Only 2% of privately insured infants had no record of WCC compared with 29% of adolescents. This contrasted with 12% of infants and 54% of adolescents who were publicly funded. Of pediatricians, <5% achieved 100% adherence to AAP guidelines for their patients (privately insured or publicly funded). Pediatricians completed an average of 52% of the recommended visits with their publicly funded patients and 68% of the recommended visits with their privately insured patients. WCC visits were underutilized for children in both managed care systems. Children of parents who have low incomes presumably could benefit greatest by preventive visits, but these children were less likely to receive the recommended number of WCC visits. Finding ways to increase the number of WCC visits that all children make is a major challenge, as is conducting studies that prove their worth.


Chapter 21: Urticaria and angioedema.
Urticaria, also known as hives, may affect up to 20% of the population at some time in their lives. Urticaria is characterized by extreme pruritus and described as erythematous, raised, circumscribed lesions with central pallor that blanch with pressure. The pathogenesis of urticaria involves mast cell activation, with subsequent release of histamine and other vasoactive mediators, leading to increased vascular permeability of postcapillary venules and development of edema, erythema, and pruritus. Urticaria is closely associated with angioedema in 40% of individuals; ∼10% of patients experience angioedema without urticaria. Urticarial lesions often are generalized with multiple lesions in no specific distribution; angioedema tends to be localized, commonly affecting the face (periorbital and perioral regions), tongue, uvula, soft palate or larynx, extremities, and genitalia. Urticaria is subdivided into acute and chronic urticaria based on duration of symptoms. Acute urticaria lasts <6 weeks and an identifiable cause may be discovered such as food products, medications (aspirin, nonsteroidal anti-inflammatory drugs, and antibiotics), or insect stings. Urticaria lasting >6 weeks is designated as chronic urticaria, and an etiology is seldom identified and thus considered idiopathic. Chronic urticaria may have an autoimmune basis. There is a well-documented association between autoimmune hypothyroidism (Hashimoto's disease) and urticaria and angioedema with higher incidence of antithyroid (antithyroglobulin and antiperoxidase) antibodies in these usually euthyroid patients. Furthermore, studies have revealed a circulating IgG antibody directed against the IgE receptor (F(Cε)RIα) or IgE in 40-60% of patients with chronic urticaria. Histamine 1-receptor antagonists (antihistamines) are initial therapy.


INTAKE OF SUGAR-SWEETENED BEVERAGES, MILK AND ITS ASSOCIATION WITH BODY MASS INDEX IN ADOLESCENCE: A SYSTEMATIC REVIEW.
To systematize literature references addressing the association of sugar-sweetened beverage (SSB) and milk intake with body mass index (BMI) in adolescents. A search was carried out in PubMed (US National Library of Medicine National Institutes of Health) and BVS (Virtual Library in Health). The descriptors used were: adolescents, young adult, beverages, drinking, obesity, overweight, BMI, and nutritional status. The following filters were applied: age ranging from 10 to 19 years, studies published in Portuguese or English language between 2011-2015. Thirty studies were selected (22 cross-sectional studies, 4 cohort studies, 1 randomized clinical trial, 1 case-control study, and 1 quasi-experimental study). There was association between the intake of these beverages and increase in BMI in 55% of all 20 studies that dealt with sugary drinks. When it came to soft drinks, 100% of studies reported association with increase in BMI. As to milk intake, only one article showed association with increased BMI. Three articles reported milk as a protection factor against increase in BMI; three studies found no association between this intake and BMI. Nineteen studies had representative samples and 20 surveys reported random samples. Among papers using questionnaires, 84% had been validated. There is no consensus in the literature about the association between SSB or milk intake and BMI in adolescents.


Proteolysis of SpolVB is a critical determinant in signalling of Pro-sigmaK processing in Bacillus subtilis.
SpoIVB is essential for intercompartmental signalling in the sigma(K)-checkpoint of Bacillus subtilis. SpoIVB is synthesized in the spore chamber and is the signal which activates proteolytic processing of pro-sigma(K) to its mature and active form sigma(K). We show here that SpoIVB is a serine peptidase of the SA clan. Expression of SpoIVB in Escherichia coli has shown that SpoIVB is able to self-cleave into at least three discrete products, and in vitro studies have shown cleavage in trans. Autoproteolysis of SpoIVB is tightly linked to the initiation of the two developmental functions of this protein, signalling of pro-sigma(K) processing and a yet, uncharacterized, second function which is essential for the formation of heat-resistant spores. In B. subtilis, SpoIVB is synthesized as a zymogen and is subject to two levels of proteolysis. First, autoproteolysis generating intermediate products, at least one of which is proposed to be the active form, followed by processing by one or more enzymes to smaller species. This could provide a mechanism for switching off the active SpoIVB intermediate(s) and suggests a similarity to other proteolytic cascades such as those found in blood coagulation.


Excessive E2F Transcription in Single Cancer Cells Precludes Transient Cell-Cycle Exit after DNA Damage.
E2F transcription factors control the expression of cell-cycle genes. Cancers often demonstrate enhanced E2F target gene expression, which can be explained by increased percentages of replicating cells. However, we demonstrate in human cancer biopsy specimens that individual neoplastic cells display abnormally high levels of E2F-dependent transcription. To mimic this situation, we delete the atypical E2F repressors (E2F7/8) or overexpress the E2F3 activator in untransformed cells. Cells with elevated E2F activity during S/G2 phase fail to exit the cell cycle after DNA damage and undergo mitosis. In contrast, wild-type cells complete S phase and then exit the cell cycle by activating the APC/CCdh1 via repression of the E2F target Emi1. Many arrested wild-type cells eventually inactivate APC/CCdh1 to execute a second round of DNA replication and mitosis, thereby becoming tetraploid. Cells with elevated E2F transcription fail to exit the cell cycle after DNA damage, which potentially causes genomic instability, promotes malignant progression, and reduces drug sensitivity.


Circadian rhythm in cardiac arrest: the Singapore experience.
There appears to be a circadian rhythm in the timing of cardiovascular and neurovascular events. The majority of studies have been conducted in western populations. This is the first study to look at the peaks and distribution of out-of-hospital cardiac arrest (OHCA) patients in Singapore. The Cardiac Arrest and Resuscitation Epidemiology Studies I and II were prospective observation studies on OHCA in Singapore from October 1, 2001 to October 14, 2004. This study analysed data for patients older than 16 years. All data was collected and recorded as per the Utstein style template. Analysis was done for each of the quadrants of the 24-hour clock: 0001-0600, 0601-1200, 1201-1800 and 1801-2400 hours. Of the 2,428 cases, 2,167 OHCA patients qualified for the final analysis. Their mean ages were in the 60s for all the four quadrants, with a male predominance. The two peaks noted were at 0800 and 1900 hours for cardiac causes of death (n = 1,591), and at 0900 and 2000 hours for non-cardiac causes of death (n = 576). At all times of the day, the majority of OHCA occurred in residences and the bystander cardiopulmonary resuscitation rate ranged from 14.6 to 24.3 percent in the different quadrants of the day. OHCA has a bimodal distribution in our local cohort of patients. The information obtained will be utilised for fine-tuning emergency medical services strategies, as we strive to improve our current survival rates for OHCA.


Effect of amino acid substitutions in the GerAA protein on the function of the alanine-responsive germinant receptor of Bacillus subtilis spores.
Spores of Bacillus subtilis require the GerAA, GerAB, and GerAC receptor proteins for L-alanine-induced germination. Mutations in gerAA, both random and site directed, result in phenotypes that identify amino acid residues important for receptor function in broad terms. They highlight the functional importance of two regions in the central, integral membrane domain of GerAA. A P324S substitution in the first residue of a conserved PFPP motif results in a 10-fold increase in a spore's sensitivity to alanine; a P326S change results in the release of phase-dark spores, in which the receptor may be in an "activated" or "quasigerminated" state. Substitutions in residues 398 to 400, in a short loop between the last two likely membrane-spanning helices of this central domain, all affect the germination response, with the G398S substitution causing a temperature-sensitive defect. In others, there are wider effects on the receptor: if alanine is substituted for conserved residue N146, H304, or E330, a severe defect in L-alanine germination results. This correlates with the absence of GerAC, suggesting that the assembly or stability of the entire receptor complex has been compromised by the defect in GerAA. In contrast, severely germination-defective mutants such as E129K, L373F, S400F, and M409N mutants retain GerAC at normal levels, suggesting more local and specific effects on the function of GerAA itself. Further interpretation will depend on progress in structural analysis of the receptor proteins.


CT of cystic renal masses: analysis of diagnostic performance and interobserver variation.
Our objective was to assess the clinical usefulness and interobserver variability of the Bosniak classification scheme for characterizing a series of pathologically proven cystic renal lesions imaged with CT. Seventy pathologically proven cystic renal masses (38 benign, 32 malignant) in 46 patients were reviewed independently by three radiologists. The cystic masses were categorized by each reviewer according to both the Bosniak classification and the receiver operating characteristic (ROC) analysis. Both the individual results for each reader and the pooled results for all three readers were analyzed. Interobserver agreement and discordance in classifying lesions as Bosniak categories I-II or III-IV were assessed. The distribution of the 70 lesions (based on the average of the three readers) was 22 Bosniak I (0% malignant), eight Bosniak II (13% malignant), 11 Bosniak III (45% malignant), and 29 Bosniak IV (90% malignant). All readers agreed on the Bosniak classification in 59%, or 41 of the 70 lesions (I, 17; II, one: III, four: and IV, 19). Eleven (16%) of the 70 lesions were classified as Bosniak I or II by one reader and as Bosniak III or IV by at least one other reader. The area under the curve for the pooled ROC analysis was calculated to be 0.957. Individual reader values ranged from 0.914 to 0.981. The sensitivities, specificities, and accuracies for the three readers ranged from 94% to 100%, 71% to 92%, and 84% to 93%. Assessment of interobserver variability by kappa analysis yielded scores of .571 and .477 for the Bosniak and ROC analyses, respectively. Overall, the Bosniak classification scheme is useful for evaluating renal masses: however, interobserver variation in distinguishing. Bosniak II and Bosniak III lesions may present difficulties in recommending surgical versus conservative management.


Probiotics: from myth to reality. Demonstration of functionality in animal models of disease and in human clinical trials.
The enteric flora comprise approximately 95% of the total number of cells in the human body and are capable of eliciting immune responses while also protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract (GIT) may also be implicated in the pathogenesis of several chronic conditions such as inflammatory bowel disease (IBD). The University College Cork-based Probiotic Research Group has successfully isolated and identified lactic acid bacteria (LAB) which exhibit beneficial probiotic traits. These characteristics include the demonstration of bile tolerance; acid resistance; adherence to host epithelial tissue; and in vitro antagonism of potentially-pathogenic micro-organisms or those which have been implicated in promoting inflammation. The primary objective of this report is to describe the strategy adopted for the selection of potentially effective probiotic bacteria. The study further describes the evaluation of two members of the resulting panel of micro-organisms (Lactobacillus salivarius subsp. salivarius UCC118 and Bifidobacterium longum infantis 35624) under in vitro conditions and throughout in vivo murine and human feeding trials. Specifically, an initial feeding study completed in Balb/c mice focused upon (i) effective delivery of the probiotic micro-organisms to the GIT and evaluation of the ability of the introduced strains to survive transit through, and possibly colonise, the murine GIT; (ii) accepting the complexity of the hostile GIT and faecal environments, development of a method of enumerating the introduced bacterial strains using conventional microbiological techniques; and (iii) assessment of the effects of administered bacterial strains on the numbers of specific recoverable indigenous bacteria in the murine GIT and faeces. Additional research, exploiting the availability of murine models of inflammatory bowel disease, demonstrated the beneficial effects of administering probiotic combinations of Lactobacillus salivarius UCC118 and Bifidobacterium longum infantis 35624 in prevention of illness-related weight loss. A further ethically-approved feeding trial, successfully conducted in 80 healthy volunteers, demonstrated that yoghurt can be used as a vehicle for delivery of Lactobacillus salivarius strain UCC118 to the human GIT with considerable efficacy in influencing gut flora and colonisation.


Treatment of acute agitation in psychotic disorders.
Several psychotic disorders, including schizophrenia, may be associated with symptoms of acute agitation and aggression. While drug treatment of agitation is often essential, non-pharmacological interventions, both environmental and behavioral, also play important roles in the complex management of agitated patients. The most extensively used psychotropic drugs are parenteral formulas of conventional antipsychotics and benzodiazepines. Recently, injection forms of two second generation antipsychotics, olanzapine and ziprasidone, have become available. Both drugs have shown adequate efficacy and tolerability in several double-blind trials of intramuscular administration in acutely agitated psychotic patients. Compared to conventional medication, injection forms of the new antipsychotics may have a faster onset of action and more favorable profile of adverse events. Alternative approaches to injection administration include liquid drug formula, orally disintegrating tablets and wafers, treatment initiation with high doses, or rapid dose escalation. Evidence suggests that second-generation antipsychotics should be among the first-line choices in the treatment of agitation in acute psychosis.


Intra- and interexaminer reliability of four manual shoulder maneuvers used to identify subacromial pain.
Shoulder pain is a diagnostic challenge and the physical clinical examination of the shoulder is crucial. It is important that the diagnostic tests used are valid as well as reliable. The objective of the study was to assess intra- and interexaminer reliability for four manual shoulder maneuvers; the Neer impingement sign, the Hawkins-Kennedy impingement test, the Patte maneuver, the Jobe supraspinatus test. These maneuvers are frequently used in clinical practice to examine patients with shoulder complaints in which subacromial pain is highly suspected. Thirty-three participants with shoulder pain were included consecutively. Within a week from inclusion, the four maneuvers were performed by a physiotherapist. The procedure was standardized in order to increase reproducibility. After a week, the maneuvers were performed again by the same physical therapist (test-retest) and by another physical therapist (test for interexaminer reliability). All four maneuvers have an almost perfect agreement (Kappa coefficients 0.91-1.00), if performed with suggested standardizations. Neer impingement sign, Hawkins-Kennedy impingement test, Patte maneuver as well as Jobe supraspinatus test, are highly reproducible and therefore reliable to use in clinical practice to identify patients with subacromial pain with an impingement phenomenon, but the maneuvers are limited as structural discriminators.


Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus.
Heterozygous mutations in p63 are associated with split hand/foot malformations (SHFM), orofacial clefting, and ectodermal abnormalities. Elucidation of the p63 gene network that includes target genes and regulatory elements may reveal new genes for other malformation disorders. We performed genome-wide DNA-binding profiling by chromatin immunoprecipitation (ChIP), followed by deep sequencing (ChIP-seq) in primary human keratinocytes, and identified potential target genes and regulatory elements controlled by p63. We show that p63 binds to an enhancer element in the SHFM1 locus on chromosome 7q and that this element controls expression of DLX6 and possibly DLX5, both of which are important for limb development. A unique micro-deletion including this enhancer element, but not the DLX5/DLX6 genes, was identified in a patient with SHFM. Our study strongly indicates disruption of a non-coding cis-regulatory element located more than 250 kb from the DLX5/DLX6 genes as a novel disease mechanism in SHFM1. These data provide a proof-of-concept that the catalogue of p63 binding sites identified in this study may be of relevance to the studies of SHFM and other congenital malformations that resemble the p63-associated phenotypes.


A more physiological alternative to total fundoplication for the surgical correction of resistant gastro-oesophageal reflux.
The incidence of mechanical complications associated with the Nissen fundoplication has prompted evaluation of an anti-reflux procedure designed to be simpler and more physiological, and encompassing a broader view of the many factors involved in the anti-reflux mechanism. Preliminary assessment of the first 100 patients with a mean follow-up of 3.5 years showed symptomatic improvement in 96 per cent and complete relief in 85 per cent. A further 100 patients were studied using formal symptom scoring, endoscopy, manometry and pH monitoring performed before operation and 3 months after operation. Similar clinical results were accompanied by improvement in endoscopic oesophagitis in 95 per cent, complete healing in 74 per cent and restoration of the pH profile to physiological levels in 84 per cent. Troublesome mechanical complications comprised a 2 per cent incidence of dysphagia, but there was no gas bloat or inability to belch or vomit, which may relate to the restoration of lower oesophageal sphincter characteristics close to those of 30 asymptomatic controls. The procedure is simpler to perform than total fundoplication, is well tolerated and is applicable to patients with reflux stricture and impaired oesophageal body motility. The results of this study support the hypotheses that effective reflux control can be achieved without total fundoplication by attention to several factors of known relevance to the anti-reflux mechanism, and that restoration of characteristics of the lower oesophageal sphincter close to physiological levels results in a lower incidence of mechanical complications.


Training of basic laparoscopy skills on SimSurgery SEP.
The aim of this study was to assess the performance curve for novices training in bimanual tissue manipulation and angled laparoscope navigation, and compare those performances with the performances of experienced laparoscopic surgeons. The Camera Navigation task with a 30 degrees angled laparoscope and the Place Arrow task of the new SimSurgery SEP virtual reality simulator were used. Fourteen medical trainees (no laparoscopy experience) performed four training sessions within one week, including 15 repetitions of each task in total. The experienced participants (>50 procedures & familiar with angled laparoscope) performed each task twice. The performance on both tasks by the novices improved significantly over the training sessions. The experienced participants performed both tasks significantly better than the novices in repetition 3. After repetition 15, the performances of the novices on both tasks were of the same level as the performances of the experienced participants. By training on SimSurgery SEP, medical trainees can extensively improve their skills in navigation with 30 degrees angled laparoscope and bimanual tissue manipulation. Further research should focus on the transfer of skills acquired on the simulator to the clinical setting. Knowledge on proficiency thresholds and training end-points for pre-clinical criterion-based training of different laparoscopic tasks also needs to be extended.


When amnesic patients perform well on recognition memory tests.
Extended exposure to study material can markedly improve subsequent recognition memory performance in amnesic patients, even the densely amnesic patient H.M. To understand this phenomenon, the severely amnesic patient E.P., 3 other amnesic patients, and controls studied pictorial material and then were given either a yes-no (Experiment 1) or a 2-alternative, forced-choice (Experiment 2) recognition test. The amnesic patients and controls benefited substantially from extended exposure, but patient E.P. consistently performed at chance. Furthermore, confidence ratings corresponded to recognition accuracy. The results do not support the idea that the benefit of extended study time is due to some kind of familiarity process made available through nondeclarative memory. It is likely that amnesic patients benefit from extended study time to the extent that they have residual capacity for declarative memory.


Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy.
Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy.


Sequential scalar quantization of vectors: an analysis.
Proposes an efficient vector quantization (VQ) technique called sequential scalar quantization (SSQ). The scalar components of the vector are individually quantized in a sequence, with the quantization of each component utilizing conditional information from the quantization of previous components. Unlike conventional independent scalar quantization (ISQ), SSQ has the ability to exploit intercomponent correlation. At the same time, since quantization is performed on scalar rather than vector variables, SSQ offers a significant computational advantage over conventional VQ techniques and is easily amenable to a hardware implementation. In order to analyze the performance of SSQ, the authors appeal to asymptotic quantization theory, where the codebook size is assumed to be large. Closed-form expressions are derived for the quantizer mean squared error (MSE). These expressions are used to compare the asymptotic performance of SSQ with other VQ techniques. The authors also demonstrate the use of asymptotic theory in designing SSQ for a practical application (color image quantization), where the codebook size is typically small. Theoretical and experimental results show that SSQ far outperforms ISQ with respect to MSE while offering a considerable reduction in computation over conventional VQ at the expense of a moderate increase in MSE.


Evaluating noise in social context: the effect of procedural unfairness on noise annoyance judgments.
General dosage-response curves typically over- or underestimate the actual prevalence of noise annoyance for specific groups of individuals. The present study applies a social psychological approach to noise annoyance that helps to understand and predict collective deflections from the curve. The approach holds that being exposed to man-made sound is more than mere exposure; it is a social experience, too: You expose Me. In effect, social aspects of the situation, like the evaluation of the sound management procedure, influence the evaluation of sound. The laboratory experiment (N=90) investigates the effect of procedural unfairness on noise annoyance. The sound management procedure is varied systematically: Participants are promised they will listen to the sound of their choice (i.e., bird song, radio sound, or aircraft sound) but receive aircraft sound despite their expressed preference (unfair procedure), or they are simply told they will listen to aircraft sound (neutral procedure). All are exposed to aircraft sound (50 or 70 dBA Leq). A collective rise in noise annoyance is predicted in the unfair relative to the neutral procedure conditions. Results show that noise annoyance ratings are significantly higher in the unfair relative to the neutral conditions. Consequences for theory and practice are discussed.


Microbial biosynthesis of medicinally important plant secondary metabolites.
Secondary metabolites derived from plants are a valuable source of pharmaceuticals, nutraceuticals, and cosmetics. To harness the potential of these natural products, reliable methods must be developed for their rapid and sustainable resupply. Microbial production of plant secondary metabolites through the heterologous expression of plant biosynthetic genes represents one such solution. This highlight focuses on recent advances in the microbial biosynthesis of plant secondary metabolites including terpenoids, flavonoids, and alkaloids as well as providing a brief insight into the current limitations and future prospects.


An investigation of entrance surface dose calculations for diagnostic radiology using Monte Carlo simulations and radiotherapy dosimetry formalisms.
Our aim in this work was to investigate the methodology used in the determination of the entrance surface dose (ESD) in diagnostic radiology. In kV x-rays for low-energy photons (tube potential up to 160 kV, HVL: 1-8 mm Al), the ESD is based on the use of the ratio of mass-energy absorption coefficients and backscatter factors. A full simulation of the photon and electron transport in a kilovoltage x-ray unit, using the Monte Carlo code BEAM/EGS4, was performed to obtain an accurate beam phase space for use in dose calculation. The modelled phase space was experimentally validated for the beam qualities (measured HVL: 3.3 mm Al-2.2 mm Cu) and showed good agreement between calculated and measured HVLs, air kerma and relative dose distributions. We have computed the conversion factors from air kerma to water or soft tissue absorbed dose at the surface of a phantom for beam qualities (HVL: 3.3-8.35 mm Al). The same model was also used to calculate the ESD in water and in soft tissue for the low-energy photon range considered. The results show that the numerical differences between the air kerma and the water kerma based backscatter factors are insignificant. The same conclusion was reached for the (mu(en)/rho) ratios, for soft tissue to air, evaluated using either the primary photon spectra or the spectra at the surface of a phantom. Furthermore, the good agreement obtained for the computation of the conversion factors with a full BEAM/EGS4 model confirms the previous studies which are based on different sources for the spectral distribution and different beam geometries (pencil beam or point source assumptions). On the other hand, the ESD in water or soft tissue is well described either with the B(air) or the B(w) formalism. Conversion factors from air kerma to ESD in these media are proposed in this work for several beam qualities in diagnostic radiology.


Control of Passion Fruit Fungal Diseases Using Essential Oils Extracted from Rosemary (Rosmarinus officinalis) and Eucalyptus (Eucalyptus agglomerata) in Egerton University Main Campus Njoro, Kenya.
Growth of fruits which form an important part of human diet has been jeopardized by the many fungal diseases that are present today. This study was conceived to isolate the most common fungal pathogens in passion fruits. Fungi were isolated using potato dextrose agar in addition to characterization using morphological, cultural, and biochemical means. Extraction of essential oils from rosemary (Rosmarinus officinalis) and eucalyptus (Eucalyptus agglomerata) was done. Before carrying the sensitivity test of essential oils to the fungal isolates, constituents of the essential oils were determined. The most common fungal pathogens isolated from passion fruits were Alternaria spp. (45%), Fusarium spp. (22%), Colletotrichum spp. (17%), and Penicillium spp. (16%). There was a relationship between heating time and yield of essential oils in rosemary (r = 0.99) and eucalyptus (r = 0.99). Conversely, there was no significant difference in the amount of essential oils produced by rosemary and eucalyptus (P = 0.08). Furthermore, there was a significant difference in growth inhibition of the fungal pathogens between essential oils from rosemary and eucalyptus (P = 0.000438). Fungal pathogens isolated from passion fruits can be controlled using essential oils from rosemary and eucalyptus. The oils need to be produced in large scale.


Construction and functional characterization of mutants of the bovine leukaemia virus trans-activator protein p34tax.
The p34tax protein [p38tax, p34, p38(XBL), XBL-I] of bovine leukaemia virus (BLV) activates transcription from the BLV long terminal repeat (LTR) promoter. To analyse the functional properties of this protein, inframe insertions and internal deletions were systematically introduced in a plasmid-encoded copy of the p34tax gene. The abilities of wild-type and mutant genes to activate gene expression from the LTR promoter linked to the chloramphenicol acetyltransferase gene and to inhibit trans-activation by the wild-type protein were studied. The trans-activating activity of 14 of the 18 mutants tested was completely abolished, but four mutants each containing a lesion in the internal portion of the polypeptide retained activity. Taken together, these results suggest the presence of an internal region of the polypeptide where structural integrity is less strictly required for the functional activity of this protein. Among the mutants incompetent in the transactivation assay, only two with mutations in the N-terminal region of the polypeptide inhibited transactivation by the wild-type protein in a dose-dependent manner. These results facilitate understanding of the physiological function of the tax protein family.


Fracture source location in thin plates using the wavelet transform of dispersive waves.
A new signal processing approach was presented for acoustic emission source location using the dispersive waves in a thin plate. For wave propagation in dispersive media, the accuracy of source location can be improved by using the arrival times of a single frequency component in the output signals at an array of sensors. The wavelet transform (WT) was used to resolve this problem. By utilizing the time-frequency data of the WT, the frequency-dependent arrival time traveling with the group velocity was shown to be easily determined. Experiments were performed using a lead break as the simulated fracture source on the surface of an aluminum plate. Two plate modes corresponding to the S(0) and A(0) Lamb waves were identified, and their group velocities were accurately measured. The source location results based on the WT method agreed well with the true locations. The WT method was also compared with the cross correlation technique, and both methods provide similar results.


A systematic review of qualitative research into people's experiences of living with venous leg ulcers.
To systematically identify, evaluate and synthesize qualitative research that examined the symptoms and health-related quality of life themes that are important from the perspective of patients with venous leg ulceration. Venous leg ulceration is a common chronic condition; the symptoms and associated treatments have a negative effect on health-related quality of life. Qualitative research methods can provide insight into the personal experiences of patients with venous leg ulceration. Qualitative evidence synthesis (using framework synthesis). Multiple electronic databases including MEDLINE, EMBASE, PsycINFO and CINAHL were comprehensively searched from inception to November 2015. Systematic identification, quality assessment and synthesis of existing qualitative research were performed; framework synthesis was conducted on included studies. An inductive approach was used and emergent themes were identified. The final stage in the synthesis involved the development of new interpretations. Thirteen studies met the inclusion criteria; the overall quality of the included studies was good. Four overarching themes were identified; physical impact, psychological impact, social impact and treatment and, in these, further subthemes were identified. Ulcer and treatment-related pain, as well as odour and exudate appeared to have significant and direct negative effects on quality of life, with additional and cumulative effects on sleep, mobility and mood. The themes identified in this review should be considered by professionals providing services, care and treatment for venous leg ulcer patients and in the selection, or development, of patient-reported outcome measures for use with this population.


A Review of Studies Leveraging Multimodal TMS-fMRI Applications in the Pathophysiology and Treatment of Schizophrenia.
The current review provides an overview of the existing literature on multimodal transcranial magnetic stimulation, and functional magnetic resonance imaging (TMS/fMRI) studies in individuals with schizophrenia and discusses potential future avenues related to the same. Multimodal studies investigating pathophysiology have explored the role of abnormal thalamic reactivity and have provided further evidence supporting the hypothesis of schizophrenia as a disorder of aberrant connectivity and cortical plasticity. Among studies examining treatment, low-frequency rTMS for the management of persistent auditory verbal hallucinations (AVH) was the most studied. While multimodal TMS/fMRI studies have provided evidence of involvement of local speech-related and distal networks on stimulation of the left temporoparietal cortex, current evidence does not suggest the superiority of fMRI based neuronavigation over conventional methods or of active rTMS over sham for treatment of AVH. Apart from these, preliminary findings suggest a role of rTMS in treating deficits in neurocognition, social cognition, and self-agency. However, most of these studies have only examined medication-resistant symptoms and have methodological concerns arising from small sample sizes and short treatment protocols. That being said, combining TMS with fMRI appears to be a promising approach toward elucidating the pathophysiology of schizophrenia and could also open up a possibility toward developing personalized treatment for its persistent and debilitating symptoms.


Scanning electron microscopy of Spinochordodes tellinii (Camerano, 1888), (Gordiacea, Nematomorpha).
There are many species of Nematomorpha which are deficiently described and therefore pose doubts about their actual taxonomic position. This is the case with Spinochordodes tellinii (Comerano, 1888), which was transferred to four different genera and has been recently considered as species incertae sedis. A female of Spinochordodes tellinii is redescribed in this work under light microscopy and Scanning Electron Microscopy. Cuticle details, shapes and areolar distribution and the features as well as the location of spiniform structures are analysed. The systematic position is discussed.


Signaling Incentive and Drive in the Primate Ventral Pallidum for Motivational Control of Goal-Directed Action.
Processing incentive and drive is essential for control of goal-directed behavior. The limbic part of the basal ganglia has been emphasized in these processes, yet the exact neuronal mechanism has remained elusive. In this study, we examined the neuronal activity of the ventral pallidum (VP) and its upstream area, the rostromedial caudate (rmCD), while two male macaque monkeys performed an instrumental lever release task in which a visual cue indicated the forthcoming reward size. We found that the activity of some neurons in VP and rmCD reflected the expected reward size transiently following the cue. Reward size coding appeared earlier and stronger in VP than in rmCD. We also found that the activity in these areas was modulated by the satiation level of monkeys, which also occurred more frequently in VP than in rmCD. The information regarding reward size and satiation level was independently signaled in the neuronal populations of these areas. The data thus highlighted the neuronal coding of key variables for goal-directed behavior in VP. Furthermore, pharmacological inactivation of VP induced more severe deficit of goal-directed behavior than inactivation of rmCD, which was indicated by abnormal error repetition and diminished satiation effect on the performance. These results suggest that VP encodes incentive value and internal drive and plays a pivotal role in the control of motivation to promote goal-directed behavior.SIGNIFICANCE STATEMENT The limbic part of the basal ganglia has been implicated in the motivational control of goal-directed action. Here, we investigated how the ventral pallidum (VP) and the rostromedial caudate (rmCD) encode incentive value and internal drive and control goal-directed behavior. Neuronal recording and subsequent pharmacological inactivation revealed that VP had stronger coding of reward size and satiation level than rmCD. Reward size and satiation level were independently encoded in the neuronal population of these areas. Furthermore, VP inactivation impaired goal-directed behavior more severely than rmCD inactivation. These results highlight the central role of VP in the motivational control of goal-directed action.


Evidence based medicine--where do articles published in local indexed journals stand?
The recent emphasis on using "evidence based medicine" for decision-making in patient care issues has prompted many publishers to mention the level of evidence of articles in their journals. The "quality" of a journal may thus be reflected by the proportion of articles with high levels of evidence, apart from other criteria. We aimed to determine the level of evidence of articles in indexed Pakistani medical journals. Two journals were selected: Journal of Pakistan Medical Association (JPMA) and Journal of College of Physician and Surgeons, Pakistan (JCPSP). Based on the information in the abstracts, all articles from 2003 and 2006 were categorized according to guidelines of Center for Evidence Based Medicine, Oxford, UK. 882 items/articles were reviewed. Of these, 270 (31%) were scientific articles within which 51% belonged to the "Therapeutic" and 25% to the "Prognostic" type. Only 27% had a high level of evidence (1 and 2) while a majority of 55% had level 4 evidence. Although there was a higher proportion of scientific research articles in JCPSP than JPMA (36% vs. 25%). no major difference in the levels of evidence was noted between the two journals, nor between 2003 and 2006. Moreover, the results were quite comparable to similar international studies. The level of evidence in articles in our leading local journals compares favourably with international literature. We recommend that levels of evidence be stated with abstracts in local journals not only to help the clinicians in making decisions on the best available evidence, but also to elevate the "quality" of these journals.


Copper-Arsenic-Sulfide Thin-Films from Local Raw Materials Deposited via RF Co-Sputtering for Photovoltaics.
The inexorable increase of energy demand and the efficiency bottleneck of monocrystalline silicon solar cell technology is promoting the research and development of alternative photovoltaic materials. Copper-arsenic-sulfide (CAS) compounds are still rather unexplored in the literature, yet they have been regarded as promising candidates for use as p-type absorber in solar cells, owing to their broad raw material availability, suitable bandgap and high absorption coefficient. Here, a comprehensive study is presented on the structural and optoelectronic properties of CAS thin-films deposited via radio-frequency magnetron co-sputtering, using a commercial Cu target together with a Cu-As-S target with material obtained from local resources, specifically from mines in the Portuguese region of the Iberian Pyrite Belt. Raman and X-ray diffraction analysis confirm that the use of two targets results in films with pronounced stoichiometry gradients, suggesting a transition from amorphous CAS compounds to crystalline djurleite (Cu31S16), with the increasing proximity to the Cu target. Resistivity values from 4.7 mΩ·cm to 17.4 Ω·cm are obtained, being the lowest resistive films, those with pronounced sub-bandgap free-carrier absorption. The bandgap values range from 2.20 to 2.65 eV, indicating promising application as wide-bandgap semiconductors in third-generation (e.g., multi-junction) photovoltaic devices.


Constitutional Mismatch Repair Gene Defect Syndrome Presenting With Adenomatous Polyposis and Cafe au Lait Spots: A Case Report.
Adenomatous polyps in the gastrointestinal system rarely occur in childhood and are accompanied by syndromes such as Familial adenomatous polyposis, attenuated familial adenomatous polyposis, and MUTYH-associated polyposis, Gardner and Turcot syndrome, and also mismatch repair (MMR) gene defects. In this article, we want to present a rare patient who had adenomatous polyposis and in situ carcinoma and was detected biallelic MMR gene defect. A 16-year-old female patient admitted with painless rectal bleeding, chronic abdominal pain, and anorexia for 1 year. Her physical examination was notable for multiple cafe au lait spots. The colonoscopic and histopathologic examination revealed multiple adenomatous polyps that one of them contains low-high grade dysplasia and in situ carsinoma. Genetic analysis revealed a homozygous mutation in the PMS2 gene [c.1164delT (p.H388Qfs*10) (p.His388GInfsTer10)] and she was diagnosed with constitutional MMR gene defect syndrome. Polypectomy was performed 4 times in 2 years period. Then, the patient's last colonoscopic examination revealed a large broad polyp in the rectum and multiple polyps in the other colon segments, and she underwent colectomy because of high risk of colorectal cancer. Adenomatous polyps are very important in childhood because of rarity. In particular, the presence of cafe au lait spots and a history of malignancy detected in relatives at an early age must be considered for CMMRD.


A simple device for growing Clostridium perfringens and its application in bacteriocin studies.
A simple device constructed of common laboratory material served as a minifermenter for the growth of Clostridium perfringens. A constant flow of nitrogen gas into a culture tube containing C. perfringens assured agitation of the culture and a mechanism for dispensing small volumes of liquid from the culture without disturbing the growth environment. The method was applied to examining the growth-inhibiting effect of bacteriocins of C. perfringens where a very economical use of radioactive isotopes was possible. The activity of some bacteriocins differed when compared with previous data obtained with stationary cultures. Two major categories of bacteriocin appear to exist for this species: those bacteriocins which block the incorporation of DNA, RNA, and protein precursors and those which interfere with the organism's cell wall.


A novel rotating electrochemically anodizing process to fabricate titanium oxide surface nanostructures enhancing the bioactivity of osteoblastic cells.
Titanium oxide (TiO(2) ) surface layers with various surface nanostructures (nanotubes and nanowires) have been developed using an anodizing technique. The pore size and length of TiO(2) nanotubes can be tailored by changing the anodizing time and applied voltage. We developed a novel method to transform the upper part of the formed TiO(2) nanotubes into a nanowire-like structure by rotating the titanium anode during anodizing process. The transformation of nanotubes contributed to the preferential chemical dissolution of TiO(2) on the areas with intense interface tension stress. Furthermore, we further compared the effect of various TiO(2) surface nanostructures including flat, nanotubes, and nanowires on bioactive applications. The MG-63 osteoblastic cells cultured on the TiO(2) nanowires exhibited a polygonal shape with extending filopodia and showed highest levels of cell viability and alkaline phosphatase activity (ALP). The TiO(2) nanowire structure formed by our novel method can provide beneficial effects for MG-63 osteoblastic cells in attachment, proliferation, and secretion of ALP on the TiO(2) surface layer.


Review of 31 cases of morphologic hepatitis in liver transplant patients not related to disease recurrence.
We examined the clinical and pathologic features of morphologic hepatitis occurring after liver transplantation (LT) that is unrelated to disease recurrence. Between February 1998 and December 2003, 704 primary LTs were performed at our center. Patients transplanted for diagnoses with low risk of disease recurrence were considered for our study (n = 282). Those with hepatitis C (HCV), hepatitis B (HBV), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) were excluded. Those with morphologic hepatitis comprised our case series and had medical records reviewed for clinical associations, duration, and outcome. Thirty-one cases were identified. They were transplanted for cryptogenic cirrhosis (n = 13), steatohepatitis (n = 12), alpha-1-antitrypsin deficiency (n = 3), tumor (n = 2), and acetaminophen toxicity (n = 1); 22 cases (67%) presented within the first 8 months post-LT (range, 0.5-72 months). Histological activity was mild in 19 and moderate in 12. Associated conditions were identified in 19 patients (57%) with 3 categories being identified: probable drug toxicity (n = 7), systemic infection (n = 4), and mechanical or hemodynamic abnormalities (n = 8). Of the 25 cases that underwent follow-up biopsy 2 to 32 months (mean, 15.5 months) after the index biopsy, 10 cases had resolution and 15 cases had persistence of the infiltrate. One patient had evidence of de novo HBV infection. Morphologic hepatitis occurred in 11% of patients at low risk for disease recurrence. Associated conditions could be grouped into three categories: drug toxicity, systemic infection, and mechanical or hemodynamic factors. Most cases did not appear to progress or improved over time, with no allograft loss occurring as a result of chronic hepatitis.


Poverty: Not a Justification for Banning Physician-Assisted Death.
Many critics of the legalization of physician-assisted death oppose it in part because they fear it will further disadvantage those who are already economically disadvantaged. This argument points to a serious problem of how economic considerations can influence medical decisions, but in the context of PAD, the concern is not borne out. We will provide empirical evidence suggesting that concerns about money influence medical decisions throughout the full course of illness, but at the end of life, financial pressure is much more likely to influence a decision to pursue or reject aggressive life-extending care than it is to influence a request for PAD. We will also address the question of whether financial pressure as a result of being poor-particularly in the context of an inadequate social safety net-robs people of their autonomy, rendering their informed request and consent invalid. We argue that it does not. We will emphasize the impracticality and injustice of rejecting the role of poverty as a legitimate factor in decision-making, the irrational distinction between PAD and withdrawal of life-sustaining care, and the more appropriate focus on the great flaws in the American health care system.


[Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial].
To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre-treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted.


Reinforcement learning versus proportional-integral-derivative control of hypnosis in a simulated intraoperative patient.
Research has demonstrated the efficacy of closed-loop control of anesthesia using bispectral index (BIS) as the controlled variable. Model-based and proportional-integral-derivative (PID) controllers outperform manual control. We investigated the application of reinforcement learning (RL), an intelligent systems control method, to closed-loop BIS-guided, propofol-induced hypnosis in simulated intraoperative patients. We also compared the performance of the RL agent against that of a conventional PID controller. The RL and PID controllers were evaluated during propofol induction and maintenance of hypnosis. The patient-hypnotic episodes were designed to challenge both controllers with varying degrees of interindividual variation and noxious surgical stimulation. Each controller was tested in 1000 simulated patients, and control performance was assessed by calculating the median performance error (MDPE), median absolute performance error (MDAPE), Wobble, and Divergence for each controller group. A separate analysis was performed for the induction and maintenance phases of hypnosis. During maintenance, RL control demonstrated an MDPE of -1% and an MDAPE of 3.75%, with 80% of the time at BIS(target) ± 5. The PID controller yielded a MDPE of -8.5% and an MDAPE of 8.6%, with 57% of the time at BIS(target) ± 5. In comparison, the MDAPE in the worst-controlled patient of the RL group was observed to be almost half that of the worst-controlled patient in the PID group. When compared with the PID controller, RL control resulted in slower induction but less overshoot and faster attainment of steady state. No difference in interindividual patient variation and noxious destabilizing challenge on control performance was observed between the 2 patient groups.


Computer assisted analysis of the chest radiograph lung area and prediction of failure of extubation from mechanical ventilation in preterm neonates.
Post-extubation chest radiographs (CXRs) are frequently requested on the neonatal intensive care unit, but it is controversial whether they generate useful information. A low lung volume assessed by measurement of functional residual capacity (FRC) post extubation has been demonstrated to predict extubation failure, which is a subsequent requirement for increased respiratory support. We have previously shown that the CXR lung area obtained by computer assisted analysis significantly correlated with FRC and, therefore, speculated that a low CXR lung area post extubation would reliably predict extubation failure. The aim of this study was to test the hypothesis by analysing CXRs from 20 infants, with median gestational age of 28 weeks (range 25-33 weeks) and postnatal age 4 days (range 1-11 days). CXRs were obtained within 4 h of extubation and were scanned and analysed using a Power Macintosh computer with a Wacom A5 Ultra pad and NIH image software. The cardiac, mediastinal and thymic shadows, and areas of perihilar and lobar consolidation were subtracted from the thoracic area to give the lung area. Seven infants failed extubation and differed significantly from the rest of the cohort only with regard to their CXR lung area, median gestational age, birth weight and postnatal age. Receiver operator characteristic (ROC) curves were constructed and the areas under each ROC curve were compared. Analysis demonstrated that a low CXR lung area and an older postnatal age were the best predictors of extubation failure. A post-extubation CXR lung area of < 8.5 cm2 had the highest specificity (100%) in predicting extubation failure. We conclude that routine post-extubation CXRs can have a useful role.


Adenosine A2A receptor agonists and PDE inhibitors: a synergistic multitarget mechanism discovered through systematic combination screening in B-cell malignancies.
Using a combination high-throughput screening technology, multiple classes of drugs and targeted agents were identified that synergize with dexamethasone (Dex) in multiple myeloma (MM) cells. Performing combination screening with these enhancers, we discovered an unexpected synergistic interaction between adenosine receptor agonists and phosphodiesterase (PDE) inhibitors that displays substantial activity in a panel of MM and diffuse large B-cell lymphoma (DLBCL) cell lines and tumor cells from MM patients. We have used selective adenosine receptor agonists, antagonists, and PDE inhibitors as well as small interfering RNAs targeting specific molecular isoforms of these proteins to dissect the molecular mechanism of this synergy. The adenosine A2A receptor and PDE2, 3, 4, and 7 are important for activity. Drug combinations induce cyclic AMP (cAMP) accumulation and up-regulate PDE4B. We also observe rigorous mathematical synergy in 3-way combinations containing A2A agonists, PDE inhibitors, and Dex at multiple concentrations and ratios. Taken together, these data suggest that A2A agonist/PDE inhibitor combinations may be attractive as an adjunctive to clinical glucocorticoid containing regiments for patients with MM or DLBCL and confer benefit in both glucocorticoid-sensitive and -resistant populations.


Review of Biological Effects of Acute and Chronic Radiation Exposure on Caenorhabditis elegans.
Knowledge regarding complex radiation responses in biological systems can be enhanced using genetically amenable model organisms. In this manuscript, we reviewed the use of the nematode, Caenorhabditis elegans (C. elegans), as a model organism to investigate radiation's biological effects. Diverse types of experiments were conducted on C. elegans, using acute and chronic exposure to different ionizing radiation types, and to assess various biological responses. These responses differed based on the type and dose of radiation and the chemical substances in which the worms were grown or maintained. A few studies compared responses to various radiation types and doses as well as other environmental exposures. Therefore, this paper focused on the effect of irradiation on C. elegans, based on the intensity of the radiation dose and the length of exposure and ways to decrease the effects of ionizing radiation. Moreover, we discussed several studies showing that dietary components such as vitamin A, polyunsaturated fatty acids, and polyphenol-rich food source may promote the resistance of C. elegans to ionizing radiation and increase their life span after irradiation.


SO3H-Containing Functional Carbon Materials: Synthesis, Structure, and Acid Catalysis.
The "sulfonated carbons" are a new class of metal-free solid protonic acids characterized by their unique carbon structure and Brønsted acidity (-H0 = 8-11) on par to concentrated H2SO4. These carbon materials covalently functionalized with SO3H groups via C-PhSO3H or C-SO3H linkages can act as versatile water-tolerant solid acids. Due to their low production costs, unique surface chemistry, high chemical and thermal stability, as well as tailorable pore structures they are regarded as potential substitutes to liquid H2SO4. Catalysis, in particular, biomass and large molecule catalysis, is one of the important areas in which acidic carbons have demonstrated exceptional activity and selectivity, outperforming traditional solid acid catalysts (cation-exchange resins, sulfated oxides, and acidic zeolites). In this review we address developments in the different types SO3H- and PhSO3H-functionalized acidic carbon materials, their structure, active sites, and surface properties, applications in catalysis, as well as activation and deactivation characteristics covering important literature since 2004. In particular, we aim to provide a systematic discussion on the specific merits and demerits of such materials obtained from different carbon precursors and functionalization methods which directly influence the structure-stability-acidic properties and catalytic performance.